Saturday, July 09, 2005

Jean Swenson: Stem Cell Tales of Hope and Hype

People who want government to fund ES cell research are expecting taxpayers to pay for science projects that knowledgeable investors will not. William Haseltine, ES cell research advocate and CEO of Human Genome Sciences said, "The routine utilization of human embryonic stem cells for medicine is 20 to 30 years hence. The timeline to commercialization is so long that I simply would not invest. You may notice that our company has not made such investments."
Those serious about clinical trials and treatments--not just basic research--are using adult stem cells or cord blood. The Spinal Cord Society (SCS), based in Fergus Falls, MN, with 200 chapters worldwide, is on the cutting edge of spinal cord applied research, meaning they're trying to find treatments that really work. SCS will be starting human trials using cells from patients' own nasal cavities. SCS leadership have said they would use ES cells "if they worked for us." But because of ES cell medical problems, SCS is currently pursuing adult stem cells and avoiding embryonic.

Thursday, July 07, 2005

Hurlbut's proposal

The Holy Fool discusses Hurlbut's proposed "altered nuclear transfer" process as a possible means of obtaining morally "untainted" embryonic stem cells. Hurlbut presented and had coverage of his thesis in several forums, including back in March when the Legionaries of Christ held a conference on stem cells, cloning and embryo adoption at the Regina Apostolorum University. John Allen's Word from Rome that week did a great job of covering the issue. Allen sums up his plan:
Another proposal for a morally legitimate avenue of research comes from Dr. William Hurlbut of Stanford University, also a member of the President's Council on Bioethics. He proposes a method called "altered nuclear transfer," which essentially means creating limited cellular systems resembling embryos but without the characteristics of "orderly existence" characteristic of human life.

In essence, the idea is to generate cellular entities more like tumors than human beings, which also produce embryonic stem cells that could be harvested for research and therapy.

They are basically trying to engineer a teratoma. It produces stem cells, but like any other tumor is not a human life.
Altered nuclear transfer mimics cellular systems such as ovarian tumors that contain stem cells. It's well documented, Hurlbut pointed out, that certain tumors can actually produce well developed body parts and organs. (He showed a slide of a tumor in a woman's ovary that actually generated a set of teeth). The idea would be to implant cells that have been altered to "turn off" certain genes essential for development into a human being, so that what results is more akin to a tumor than human life.

Many in the pro-life and scientific community became aware that there was a problem with this procedure. Are we sure that we are not creating life? Are we sure that we aren't just creating embryos pre-set to die? In other words are we still creating life for the sole purpose of destroying it?
Dominican Fr. Nicanor Austriaco, who holds a Ph.D. in biology from MIT, ...said, however, that rather that engineering a gene to turn off after some period of normal development, he would be more comfortable with altered nuclear transfer if something were altered from the very beginning, such as the disruption of the embryonic axes. ...

In response to Hurlbut, Eric Cohen of the Washington, D.C.-based Ethics and Public Policy Center asked rhetorically if the entity envisioned by altered nuclear transfer is really just a cellular system, or an embryo "pre-programmed to die."

The New England Journal of Medicine added:
Hurlbut's argument for the ethical superiority of altered nuclear transfer rests on a flawed scientific assumption. He argues, on the basis of supposed insights from systems biology, that it is acceptable to destroy a CDX2 mutant embryo but not a normal embryo, because the former has "no inherent principle of unity, no coherent drive in the direction of the mature human form." But these are ill-defined concepts with no clear biologic meaning, and an alternative interpretation would be that embryos lacking CDX2 develop normally until CDX2 function is required, at which point they die. Philosophers may debate these and other interpretations. We see no basis for concluding that the action of CDX2 (or indeed any other gene) represents a transition point at which a human embryo acquires moral status.

It seems the latest proposal has attempted to take these criticismst into consideration. By attempting to reprogram the entity to keep the cells at a pluripotent stage rather than the totipotent stage of a true zygote. If the cells are never totipotent then they never have the capacity to produce the whole, do they?
The Production of Pluripotent Stem Cells by Oocyte Assisted Reprogramming
Joint Statement
puts it this way:
The ability to clone animals, such as Dolly the sheep, by transfer of a specialized adult nucleus to an enucleated oocyte demonstrates the power of epigenetic reprogramming: the oocyte cytoplasm is sufficient to reprogram the somatic nucleus to a totipotent state. Human cloning has been proposed as a means of generating human embryos whose pluripotent stem cells would be used in scientific and medical research. Here, through a form of altered nuclear transfer, we propose to utilize the power of epigenetic reprogramming in combination with controlled alterations in gene expression to directly produce pluripotent cells using adult somatic nuclei, without generating and subsequently destroying embryos.

I have a couple of comments:

1. This proposal still lies in the realm of pure theory. It has worked on mice cells, by "turning off" a certain protein, but most scientist do no think it will be so easy to reproduce in humans. It will take more than "turning off" a single protein to prevent formation of a "true" embryo. In the meantime, the other side insists that this proposal is purely diversionary and will keep on studying other promising avenues of embryonic research. It ain't stoppin' them.

2. Where will the eggs come from? Once again, we are looking at needing millions of eggs - unless we can obtain them from stem cells (the science is still way out on this one too.) So what underdeveloped nation do we turn into an egg farm? Whose poor women do we exploit first?

If we are looking for ethical approaches with a minimum of other concerns, then why not research more on "dedifferentiation" - reprogramming multipotent adult stem cells into pluripotent embryonic cells. Eggs

William Hurlbut on Altered Nuclear Transfer

"Some have raised the objection that we may be just creating a 'disabled' embryo. This is a serious consideration, but I believe the recent proposal for ANT-OAR has fully met these concerns. This method would turn on certain master genes that define ES cells but which are never on in a fertilized egg. By fast-forwarding to the gene expression pattern of a pluripotent cell we would bypass the embryo and go directly to a differentiated cell type. A human embryo has a developmental potential; it is that stage at which the whole produces the parts. Without the capacities to form the basic body axes and body plan, a growing thing is simply not an organism, but merely a trajectory of disorganized growth. There is a proof in nature that you can get embryonic stem cells without an embryo. Naturally occurring ovarian tumors called teratomas can produce all the primary embryonic cell types and even more advanced tissues and body parts, but no physician would consider a teratoma a living being. Embryonic stem cells, likewise, lack the capacity to form an organism (they produce teratomas when implanted into the human body), so they too are not embryos. To be a human embryo means to have a coherent unity and a developmental potential along the trajectory of the human form. " (source)