Coming Home

My article in today’s Headline Bistro.

As soon as scientists begin discussing the differences between embryonic stem cells, adult stem cells, induced pluripotent stem cells, and altered nuclear transfer, most non-scientists become overwhelmed by the technicalities and quickly lose their moorings in the ethical and funding debates. This is needless and easily cleared up with a simple analogy.

Imagine one is dining in a family restaurant and there are three different families, each with five children. Family A has children who are engaged in a food fight, screaming, and jumping about.

Family B has children who are generally very well behaved, but are given to bouts of restlessness and need to be spoken to by their parents.

Family C has children who are models of decorum, and who on their own have even taken it upon themselves to quietly clean up some of the mess left by other patrons.

That’s the stem cell war in a nutshell. Family A are the embryonic stem cells, wild and untamed, wreaking havoc everywhere they are introduced. They are beyond the ability of scientists to control, and have created tumors in animals during that phase of testing. There is one clinical trial underway in humans we shall return to in Part II.

Electron Micrograph of Early Embryo on the Head of a Pin

Family B are the induced pluripotent stem (iPS) cells. These are normal body cells such as cheek cells and skin cells that have undergone full adult development and then have been chemically treated to return to a state where they can be redirected to become other types of body cells. The problem with these cells is that they have shown some degree of instability, with a propensity to return to their fully differentiated adult state. More on that in a moment.

Family C are the adult stem cells. These are cells that have undergone a great degree of development from the early embryonic stage of development and have the ability to become certain types of tissue. They are remarkably stable when used, and have repeatedly proven themselves remarkably adaptable in clinical trials and therapeutic application. There are over one hundred therapies using these cells.

Now, back to our analogy. Imagine a reporter from an international news agency such as Reuters comes to the restaurant looking to do a story on children’s manners in restaurants and actually spends 90% of her time interviewing the father of Family A, who makes not one mention of his children’s recklessness and destructiveness, not one mention of the exemplary behavior of the children in Family C, but holds forth on the dire future of the children in Family B whose behavior is merely in need of periodic tweaking.

If that sounds unbalanced and bizarre, that’s the essential structure and trajectory of a recent Reuters article by Julie Steenhuysen, entitled, ANALYSIS-Imperfections Mar Hopes for Reprogrammed Stem Cells. The article may be read here.

The core of the article is built around the father of Family A, Dr. George Daley of the Harvard Stem Cell Institute. This quote from Dr. Daley sums up the art of the dodge by proponents of embryonic stem cell research:

“It has not ever been a scientifically driven argument that iPS cells are a worthy and complete substitute for embryonic stem cells,” Daley said. “Those arguments were always made based on political and religious opposition to embryonic stem cells.”

Yes and no.

It’s true that there are people who find it an abhorrent practice to juice women up with dangerous levels of hormones in order to harvest a clutch of eggs from her, fertilize them in a lab, create new human beings and then tear them apart in their embryonic stages of development for the purpose of benefiting other human beings. So, yes there are those who object on political, religious and ethical grounds to such barbarism.

Dr. Daley makes no mention at all of Family C, the adult stem cells which have over one hundred therapeutic applications. In so doing, he fails to grasp the essential reason why induced pluripotent stem cells were sought after. It’s because biologically, embryonic stem cells are wild and untamable, while adult stem cells have gone through the process of cellular maturation naturally and are remarkably stable. They are also expensive to isolate, which is an economic limitation to their widespread use. Also, as embryonic stem cells come from another person, there is the issue of tissue rejection by the recipient.

iPS cells were developed to take advantage of the stability that comes with being a mature cell, and both the abundance of such cells (i.e. skin cells) and their ease of isolation. The thought has been that a few tweaks could get the cells to revert to an earlier developmental stage, as every cell has an identical set of genetic switches. By resetting the switches in the DNA, we have been able to get these cells to revert to an earlier, embryonic stage of malleability, yet retaining much of their adult stability. Also, as the cells come from the patient, there is no issue of tissue rejection.

It seems that some of these cells have a propensity to revert to their adult form. This instability differs from the instability of the embryonic stem cells in one key respect. When an iPS cell reverts to adult form, therapy fails and the cell dies. The difficulty with embryonic cells is that they tend to form tumors, which adds a whole new disease state to the patient.

As the state of the research exists, it is far easier to tweak the behavior of the iPS cell than it is to bring any semblance of order out of the primordial chaos of embryonic stem cells. The difference?

As the human body develops, cells mature under the influence of immediately neighboring and distant cells in the body. We know a small degree of how this happens, and embryonic stem cell research allows us to attempt this in the Petri dish. It is a daunting task to take a few early cells from a young embryo and replicate blindly the phenomenally complex processes of maturation that occur in the context of an integrated organism.

Tweaking the iPS cell is the easier and morally superior approach.

In Part II, where each technology stands in its development and what therapeutic trials and applications each has underway.