Commentary: Facing up to the feasibility of ANT-OAR.

This issue of Stem Cell Reviews features an uncommon genre of scientific expose. In his critical evaluation of recent proposals for altered nuclear transfer with oocyteassisted reprogramming (ANT-OAR), Malcolm Byrnes probes the scientific feasibility of the ANT-OAR concept. Byrnesâ commentary may initially strike readers as out of place in a journal whose mission is to provide critical scientific perspectives on developments in stem cell biology. However, because ANT-OAR is currently undergoing active discussion as a strategy to replace existing methods of human embryonic stem cell derivation, which many consider unethical, Byrnesâ critical assessment of the feasibility of ANT-OAR is not only appropriate, but it is also quite timely. ANT-OAR has been proposed as a method for genetically engineering somatic cells, so that, when their nuclei are transplanted into enucleated oocytes, they yield cells that divide to become embryonic stem cells before initiating a human zygote with potential to develop into a multicelled human being. Arguments about the expected nature of the embryology and humanity of cells genetically engineered by such envisioned techniques have raged since the ANT-OAR concept first came to public notice. Byrnes leaves these formidable moral and ethical questions to others and focuses his attention instead on the question of whether ANT-OAR is likely to be accomplished at all, given the current state of knowledge for embryonic stem cell molecular biology. Byrnes_s scientific argument that the ANT-OAR concept is highly speculative is cogent and sound. Clearly, the complex nature of Nanog expression and function certainly makes the ANT-OAR proposal appear a naїve one, when it comes to the likelihood of successful implementation of its theoretical concept. Moreover, Byrnes emphasizes that our general knowledge on the complex network nature of gene regulation in mammalian cells makes the proposal that any master regulator exists, that can effect the prescriptions for successful ANT-OAR, a dubious one at best and a misleading one at worst. Byrnes_s critical analysis calls on the involved scientists to face up to their responsibility for complete disclosure of the feasibility of ANT-OAR. In cases of public debate on the responsible conduct of research involving human subjects, the quality of scientific disclosure is crucial to achieving valid, productive discourse. If scientists know that, based on scientific knowledge, ANT-OAR is highly speculative or implausible, then good ethics require the full disclosure of this caveat in the public debate. Byrnes points out that only stating that future research may yield currently unforeseeable advances is neither sufficient nor ethical. Unlike discovery research, ANT-OAR is an engineering proposal; and, as such, it must be evaluated in terms of the likelihood that it can be accomplished given existing knowledge. The belief that ANT-OAR can be achieved has become a significant driver for increasing public support for human embryonic stem cell research. Thus, its social impact reaches far beyond the laboratories of investigators pursuing it. The promotion of an ANT-OAR public persona of certain accomplishment, when promoting Stem Cell Rev (2007) 3:66–67 DOI 10.1007/s12015-007-0013-7