Stem Cells from Skin Cells: The Ethical Questions

Recently, research teams led by Shinya Yamanaka and James Thomson published separate reports that they had genetically modified human skin cells to behave like embryonic stem cells.¹ Like their embryonic counterparts, these induced pluripotent stem cells (iPS cells) were capable of forming all three germ layers both in vitro and in immunodeficient mice, demonstrating their remarkable pluripotential character. Furthermore, the two teams' iPS cell colonies were genetically matched to the human skin cells from which they were derived, thus enlivening the possibility that one day (perhaps soon) patient- and disease-specific pluripotent stem cells could be generated for research that could later yield downstream clinical benefits.

Now that human iPS cells have arrived, many will wonder whether the thorny ethical challenges surrounding stem cell research can be fortuitously bypassed. This is hardly the case. While the scientific possibilities of iPS cells are enormously exciting, human iPS cell research raises both new ethical complexities and old philosophical problems.

As colleagues and I have noted elsewhere, it would be a serious mistake to conclude that iPS cell research averts the need for human embryonic stem cells.² Human iPS cell research must proceed together with human embryonic stem cell research for many important reasons.

Ongoing research on human embryonic stem cells is necessary to inform scientists' growing understanding and analyses of human iPS cells. Much more work is needed on both iPS cells and embryonic stem cells to determine whether these two kinds of stem cells differ in biologically and clinically significant ways.³ As a matter of fact, we do not know at this point which of the possible sources of disease-specific pluripotent human stem cells—genetically screened IVF embryos, iPS cells, somatic cell nuclear transfer into enucleated oocytes,⁴ or somatic cell chromosome transfer into zygotes and blastomeres that have had their own chromosomes removed⁵—will prove to be the best for clinical applications, all other things considered.

Safety is also a major concern for human iPS cells since the retroviruses used to insert the pluripotency-inducing genes might themselves lead to cancer and other harmful mutations (one of the pluripotency-inducing factors Yamanaka's group used was c-Myc, a gene commonly associated with tumor formation). In contrast, human embryonic stem cells are the only pluripotent human cells that are genetically unmodified; they are pluripotent stem cells in their purest, unadulterated form. Thus, in addition to possessing enormous scientific value in their own right, embryonic stem cells will be needed to serve as controls for examining the safety and efficacy of human iPS cells.⁶

Prudence calls for all research alternatives to be pursued simultaneously if possible. The idea that iPS cell research can (and should) proceed by itself is not a hope that makes much scientific sense. Good science is supposed to leave no stone unturned, subject to rigorous standards of research ethics.

This brings us to my next point. The pursuit of human iPS cells raises new challenges for the process of informed consent in biomedical research. That a person must provide voluntary and informed consent before participating in a scientific study is a well-known international principle of research ethics. According to stem cell research guidelines issued last year by the International Society for Stem Cell Research, all body cell donors or their legally authorized guardians must give their contemporaneous informed consent for the use of the donors' somatic tissues in stem cell research, with a few notable exceptions.⁷ These exceptions largely pertain to the use of stored tissue samples, which would be a desirable and convenient resource for iPS cell studies. According to ISSCR guidelines, tissue samples may be used for research without contemporaneous informed consent only if researchers procure somatic cells from a tissue bank whose consent documents specifically designate nuclear reprogramming methods for stem cell research as one of the possible uses of the donor's tissues, and if donors have specifically agreed to this possible use. Only in extremely rare cases may the requirement for specified informed consent be waived. In these exceptional cases, there must be no reasonable and adequate alternative source for the unique characteristics...