'Pluripotent' Stem Cell (iPS) Research is Not the Usual 'Adult' Stem Cell Research

Dianne N. Irving
Copyright April 8, 2009
Reproduced with Permission

An "exciting" new method of producing human "stem cells" to cure Parkinson's and many other debilitating diseases was recently announced as "breaking news" on U-tube (Dr. Oz to Oprah and Michael J Fox: "The stem cell debate is dead". The video proceeded to be passed around the world at the speed of light. The new research explained by Dr. Oz to Oprah in this video is referred to as "induced pluripotent stem cell" research (iPS research). As Dr. Oz noted, an adult human cell (e.g., a patient's own skin cell) can be transformed or induced from a very differentiated state back to a relatively less differentiated state to form an "embryo-like" human cell that is "pluripotent" (capable of forming most of the cells, tissues and organs of an adult human being). These new iPS human cells could then possibly be urged to develop forward to produce more mature differentiated human cells for therapeutic purposes. But three things are important to distinguish before iPS research is so enthusiastically embraced as an "ethical alternative to human embryonic stem cell research".

First, iPS research is not equivalent to "adult stem cell research". The starting material (a human adult or mature body cell) may be the same, but what happens after that is very different. In the typical adult human stem cell research that has been reported for many years now, and which truly is an ethical alternative to human embryonic stem cell research, the adult human cell is not transformed or induced back to a pluripotent human "embryo-like" stem cell. Rather, these adult human stem cells are already found naturally in the human body and are simply urged to develop to a more mature state. No problem.

In iPS research, however, the highly differentiated DNA in the adult human cell that is used as the starting material is transformed or induced (by various means) back to the state of differentiation of the DNA as found in human embryonic pluripotent "stem cells". These "embryo-like" human pluripotent "stem cells" are then urged to become more mature in order to develop human cells for therapies.

Second, there are many scientific and ethical problems with iPS research that must be resolved before such research can be considered as "an ethical alternative to human embryonic stem cell research". Perhaps Dr. Oz's use of the term "embryo-like" might provide a clue. Are these iPS cells just "embryo-like", or are they - at least sometimes - really single- or multiple-cell early human "embryos", or even human totipotent cells that have the natural capacity to revert back to new whole human embryos? That is, are all of these cells truly just pluripotent, or are some of them totipotent (and thus early human embryos, or capable of reverting to new whole human embryos)?

The issue here involves requiring an honest debate, for a change, using scientifically accurate terms and the provision of all relevant details of the research - especially by the professionals involved. Otherwise any serious ethical analysis is impossible. In fact, perhaps any serious scientific analysis is impossible as well. For many years now the debates on human embryonic stem cell research have been falsely framed by proponents of such research by insisting that these human "stem cells" are all pluripotent (only capable of producing some of the cells, tissues and organs of an adult human being); that is, they claim, that these "stem cells" could not form new whole human embryos. But this is absurd "science", and the rest of the world knows it. (See list of references from Irving, "Framing the Debates on Human Cloning and Human Embryonic Stem Cells: 'Pluripotent' vs. 'Totipotent'". This article contains over 30+ pages of references documenting that these "stem cells" are often totipotent, not pluripotent -- taken from textbooks, journals, university websites, scientific/medical professional societies, university research centers, the U.S. government (including NIH!), state, national and international commissions, law schools and journals, IVF center websites, IVF textbooks, on-line encyclopedias, on-line magazines, bioethics centers, technology websites, and various books).

In the earliest developing human embryo, there is a range of both totipotent and pluripotent cells - beginning with all totipotent cells and including pluripotent cells more and more as the new human organism develops and grows bigger. By the time that the new human being reaches the blastocyst stage (5-7 days), the inner cell mass of the human blastocyst still contains a mixture of totipotent and pluripotent cells. It is more often these human embryonic cells from the inner cell mass of the human embryo that are touted as "pluripotent stem cells". But not all of them are pluripotent. Many of them are still totipotent - and the proof of the pudding is in naturally occurring human monozygotic twinning in vivo. About 2/3rds of such human twins are reproduced at the blastocyst stage. Twinning couldn't even happen if there were no totipotent cells in the human embryo's inner cell mass!

The point is that, as with the usual human embryonic "stem cells", at least some of these iPS cells that are produced are most probably also totipotent - and thus are capable of reverting to new whole human embryos by means of the natural biological process of "regulation" (as happens even in natural monozygotic human twinning). Not only that, it is also possible that human embryonic germ line cells could be reproduced in the process of transforming/inducing. These human embryonic germ line cells are slightly more mature than those in the inner cell mass of the human embryo, but have been detected as early as 2  weeks post the human embryo's biological beginning and these human embryonic germ line cells are also totipotent - and thus could also revert back to new whole human embryos. Any human embryos that are reproduced directly or indirectly in the process of doing iPS research would be destroyed.

Third, there are quite a number of other ethical concerns involving iPS research - most of which proponents also prefer to dodge. Given the obvious concerns about new whole living human embryos being directly or indirectly produced in the process, what about any ethical problems with the sources of many of the materials used during iPS research? Are any living human embryos or fetuses killed and destroyed in order to make these "materials"? For example, usually such human "materials" are involved in the various kinds of culture media used, in the DNA chips, and in the assays and other tests performed to insure that these cells are "pluripotent". Even proponents of this research admit this. Interestingly, however, there are no tests or assays to determine if any of these cells are totipotent! Sure would be helpful. Human embryonic and fetal "materials" are also used as "feeder cells", and as sources of genes used to infect and transform the adult cells. Patients also need to be concerned about any serious immune rejection reactions caused by the DNA in these iPS cells being mutated or changed (even a little bit), or by any number of other chemicals and other products used during the transformation process - even if the patient's own cells were used as the starting materials. (For an example of a far more detailed analysis of some iPS research protocols, see Irving, href="http://www.lifeissues.net/writers/irv/irv_127concerns.html">"Ethical and Scientific Concerns About Induced Pluripotent Stem Cell Research -- Yamanaka and Thomson" (June 1, 2008)).

It is long past time to get straight, complete and accurate answers out of proponents of iPS and other human embryonic stem cell, human cloning, and human genetic engineering research. Society's trust in their professional scientific credibility depends on it. But all we get is "fuzzy accolades", "hype", deconstructed "science", snickers, cheap shots, and demeaning innuendos -- or silence. It's as simple as this. Everyone deeply and sincerely hopes that some research somewhere will find these desperately needed cures. But such success must not come at the expense of the willful killing and destruction of whole living innocent human beings. This is no "ethical alternative to human embryonic stem cell research". Haven't we been there before?