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The purpose of this blog is to stimulate thought and discussion about important issues in healthcare. Opinions expressed are those of the author and do not necessarily express the views of CMDA. We encourage you to join the conversation on our website and share your experience, insight and expertise. CMDA has a rigorous and representative process in formulating official positions, which are largely limited to bioethical areas.

Techno-Babies: Some Assembly Required?

November 10, 2016

by David Prentice, PhD

Science fiction is no longer fiction—the first three-parent baby was born a few months ago. Last month in The Point, Dr. Robert E. Cranston raised a series of important questions about the safety and ethics of the technique; now more information—and more questions—have arisen. As a reminder, the concept of creating a baby with three parents came as a proposal to “treat” individuals with mitochondrial genetic diseases, i.e., mutations in the mitochondrial DNA that lead to sometimes lethal physiological problems. Sadly, the proposals do not actually treat anyone with these conditions, but rather endeavor to construct new individuals who hopefully do not carry the mutations (diagrams and discussion of these cloning, i.e., “nuclear transfer,” techniques can be found at the Charlotte Lozier Institute website.) Dismissing the patients and trying to produce unaffected humans as replacements is hardly a compassionate medical advance.

As Dr. Cranston noted previously, the new three-parent baby was created by Dr. John Zhang of New Hope Fertility Center in New York. But as Dr. Zhang admitted, the embryo creation and transfer to the womb were done in Mexico to bypass the legal restrictions imposed by the U.S. Congress (although the timing of the birth indicates the U.S. law was not in place at the time Zhang performed the laboratory creation of the three-parent embryo and the embryo transfer.) Apparently the desire to be “first” to perform this new human experiment was so strong that neither ethics nor legality could be considered a restraint on ambition. We now know this is not Dr. Zhang’s first attempt at creating a three-parent child. He recently published a paper describing his attempt in 2003 in China to do nuclear transfer between single-cell embryos, create three-parent embryos and then gestate the newly-created embryos. Little detail is provided, and none of the embryos transferred to the womb survived to term. An accompanying editorial points out there are still deficiencies and unknowns in the report, including significant questions about any ethical review.

The announcement in September, of the three-parent child’s birth earlier this year, was apparently timed due to publication of the abstract of the experiment, with the work scheduled to be presented by Dr. Zhang at the ASRM meetings in October. Even with the meeting presentation past, significant questions still remain about the details of the protocol and the extent of any ethical review. Zhang created at least five three-parent embryos, but only one embryo had a normal chromosomal karyotype; that embryo was transferred to the womb and survived to term. At this point, only a few months old, the child appears healthy but still has not received a thorough physical and long-term outlook is unknown. A second meeting abstract from Zhang’s group indicates several women were recruited to donate “healthy” eggs and at least 32 three-parent embryos were created at some point in the experiments, though only about half had normal chromosome number. For the one born three-parent child, initial tests show there is still some residual mitochondrial DNA mutation present, retained in the nuclear transfer procedure. In the few tissues sampled, on average only 5 percent mutated mitochondrial DNA was present, but laboratory tests suggested the percentages can increase substantially over time. This little child will continue to be an experiment in progress for the rest of his life.

Unfortunately, this child is the first of what may be a tidal wave of techno-babies. Reports now show another three-parent child may have been born in China, and two more three-parent babies gestating in Ukraine. The practitioners of this cloning and embryo manipulation technology are pushing ahead.

One essential ingredient in creation of three-parent embryos (or any embryo!) is an egg. Given the relative inefficiency of the three-parent embryo technique and other cloning techniques, a large number of eggs is necessary. In fact, the paucity of egg donors has been a continual complaint of the cloners, that they can’t solicit enough women as egg donors and the eggs are not of sufficient quality. The number and quality of eggs necessary for these experiments was pointed out again by the Oregon group who, in 2013, were first to create cloned human embryos and get them to survive long enough to be destroyed for their embryonic stem cells (note that these cloners are also among the chief proponents for creation of three-parent babies.)

Now Japanese scientists report they have created artificially-derived eggs from mouse skin cells and were able to fertilize some of the artificial eggs to produce born mice. Some consider this a significant advance, stating that artificial human eggs might lead to discoveries about early human development or potential treatments for infertility. But this news also raises the specter of large numbers of eggs created for human experiments.

An examination of the science shows the prospect for creating artificial human eggs from skin or other cells is unlikely for quite some time. Despite the few born mice, the production of artificial eggs in the laboratory was extremely inefficient and produced mostly abnormal eggs. The technique started with an ethical step—the creation of induced pluripotent stem (iPS) cells from mouse-tail skin. These iPS cells show the same pluripotent stem cell characteristics as embryonic stem cells, but they can be created from any cell without the life-destroying requirement necessary for embryonic stem cells. Then they stimulated the iPS cells to form immature egg cells (primordial germ cells) in the laboratory. These steps had actually been done before, including by this research group, but production of something similar to a mature egg required implanting the immature egg cells into mouse ovaries.

To get mature egg cells in the petri dish, the immature precursor cells had to be grown in the presence of mouse fetal tissue from ovaries. This is hardly a significant feat, because the use of fetal tissue demonstrates researchers still don’t know the crucial stimulatory factors necessary for egg development. When embryos were created by fertilizing mature, artificial mouse eggs with mouse sperm, some of the embryos could be gestated and resulted in newborn mice. However, the quality of the artificial eggs is questionable; the usual result was severely abnormal animals, and less than 1 percent of the total number of embryos successfully made it to birth. A number of the embryos also showed development of enlarged placentas, similar to that seen with cloned embryos. The technique would be unsafe not only for the individuals created using artificial eggs but also for the surrogate mothers who carried them.

While artificial human eggs are thus still far off, the potential for their creation and use in large-scale experimentation is the signal concern. The idea that mass-produced, laboratory-generated human beings can be created by various techniques, manipulated and destroyed for experimental curiosity, is an attitude that goes against the very grain of human dignity and freedom. Human beings are not commodities to be manufactured; each is a life with inherent worth.

David Prentice, PhD

David Prentice, PhD

David A. Prentice is Vice President and Research Director for the Charlotte Lozier Institute. He is also Adjunct Professor of Molecular Genetics at the John Paul II Institute, The Catholic University of America and was a Founding Advisory Board Member for the Midwest Stem Cell Therapy Center, a unique comprehensive stem cell center in Kansas that he was instrumental in creating. In 2020, he was appointed by the Secretary of HHS to the federal Human Fetal Tissue Ethics Advisory Board. Dr. Prentice has over 40 years’ experience as a scientific researcher and professor, including previous service as senior fellow for life sciences at the Family Research Council, Professor of Life Sciences at Indiana State University, and Adjunct Professor of Medical and Molecular Genetics, Indiana University School of Medicine.

He established Stem Cell Research Facts, an educational website providing scientific facts and patient-centered videos about adult stem cells, and is a founding member of Do No Harm: The Coalition of Americans for Research Ethics, and an advisory board member for the Center for Bioethics and Human Dignity. He has provided scientific advice for numerous medical professionals, legislators, policymakers and organizations at the state, federal, and international levels.

Dr. Prentice received his Ph.D. in biochemistry from the University of Kansas, and was at Los Alamos National Laboratory and the University of Texas Medical School-Houston before joining Indiana State University where in addition to his research and teaching, he served as Acting Associate Dean of Arts and Sciences and Assistant Chair of Life Sciences. He was recognized with the University’s Caleb Mills Distinguished Teaching Award and Faculty Distinguished Service Award. He has taught courses ranging from non-majors biology to advanced and graduate courses including developmental biology, embryology, cell and tissue culture, history of biology, science and politics, pathophysiology, medical genetics, and medical biochemistry. Several of his courses were also taught on-line.

He received the 2007 Walter C. Randall Award in Biomedical Ethics from the American Physiological Society, given for promoting the honor and integrity of biomedical science through example and mentoring in the classroom and laboratory. Dr. Prentice’s research interests encompass various aspects of cell growth control, cell and developmental biology; one major focus is adult stem cells. He has reviewed for various professional publications including The Journal of the American Medical Association.

He is an internationally-recognized expert on stem cell research, cell biology and bioethics, and has provided scientific lectures and policy briefings in 40 states and 21 countries, including testimony before the U.S. Congress and numerous state legislatures, the U.S. National Academy of Sciences, the President’s Council on Bioethics, European Parliament, British Parliament, Canadian Parliament, Australian Parliament, German Bundestag, French Senate, Swedish Parliament, the United Nations, and the Vatican. He was selected by President George W. Bush’s U.S. President’s Council on Bioethics to write the comprehensive review of adult stem cell research for the Council’s 2004 publication “Monitoring Stem Cell Research.”

Dr. Prentice has published numerous scientific and bioethics articles, including a recent review of stem cell science and adult stem cell treatments published in Circulation Research. He has also published numerous commentaries and op-eds, and travels nationally and internationally to give frequent invited lectures regarding stem cell research, fetal tissue research, gene editing, cloning, embryology, cell culture and vaccines, bioethics, and public policy. He has been interviewed in virtually all major electronic and print media outlets, including CNN, ABC, NBC, CBS, Fox, CSPAN, Reuters, AP, NPR, USA Today, BBC, The Washington Post, The Los Angeles Times, and The New York Times.