From the moment physicians take the Hippocratic Oath to “do no harm,” they commit themselves to ethical decision-making in their profession. As colleagues, one a physician and one a bioethicist, we want to call attention to the importance of ethics in medical research, particularly in the case of cutting-edge reproductive technologies—cloning and parthenogenesis—currently being developed in animals.
Another baseline ethical principle regarding scientific reproductive research is “just because we can, does not mean we should.” This principle means that there needs to be a medical or research application when experimenting with new biotechnologies. Because reproductive medicine can often elicit ethical problems (e.g., raising questions about who a child’s legal parents are), any research application of reproductive technology must offer specific benefits for human health or human infertility to be worthy of continued development. If we use this lens to evaluate certain new reproductive techniques, they don’t, yet, all make the cut.
Ethical concerns emerge from the prospect of human cloning and generating human embryos via parthenogenesis—meaning the reproduction of any organism from an unfertilized egg. Ethical issues associated with cloning erupted when Ian Wilmut reported the cloning of Dolly the sheep in 1997, and the technology has continued to progress over the last 25 years despite persistent concerns about the prospect of applying it to people. Researchers, for example, have been able to clone 581 mice from a single cell without a clear medical application of how this technology would improve human health or combat infertility in ways that are both ethical and safe.
Furthermore, cloning human offspring will be prohibitively expensive, and unless covered by health insurance, would be available only to the wealthy. Right now, it costs $50,000 to clone a pet dog and $35,000 to clone a cat according to ViaGen, a company that offers this service. With such high costs for cloning pets, cloning human beings clearly would be unaffordable to the vast majority of people. Therefore, reproductive cloning doesn’t meet the medical ethics standard of justice—that medical interventions to treat disease must be financially accessible to all.
Like cloning research, a recent article in PNAS on parthenogenesis raises ethical red flags. The study represents an amazing scientific achievement: generating a mouse pup from unfertilized mouse eggs without using any sperm. In this case, two eggs from the same mouse were fused into one cell and then treated with the gene editing technology CRISPR. The modified embryos were transplanted into surrogate mothers that gave birth to viable, full-term offspring. Not only were mice created without fathers, but this “immaculate conception” process created a litter of mice pups that were identical genetic clones of their mother.
There is no scientific reason why this uniparental technology could not be used to generate cloned human embryos, but there are ethical reasons why it should not. There is a great deal of controversy about whether human beings need to be created using both an egg and a sperm. Thirty years ago many scientists believed that a human embryo was based on a purely biological fact—fertilization. Similarly, both Catholic and Judaic traditions hold that a human being needs to be created using an ovum and sperm. After the cloning of Dolly, the traditional definition of a human embryo was challenged because it was possible to create human beings through procedures other than fertilization.
Reproductive processes that work within nature are those that have been incorporated into the evolution of human life. Parthenogenesis, like cloning, represents a nontraditional reproductive technology that is not employed by any mammals. The ethical concern here is that employing such biotechnologies that work against nature may challenge how we evolve as a species. Thus, deriving a living human being from parthenotes is, in our opinion, unethical. In addition, we need to address the issue of how to define a human embryo as addressed by the ISSCR Guidelines for Stem Cell Research and Clinical Translation. They state that a human embryo is “formed by fertilization of a human oocyte by a human sperm, including an oocyte and/or sperm generated by [in vitro gametogenesis].” However, these guidelines also raise ethical concerns about forming a parthenogenetic human without the contribution of human sperm.
Parthenogenesis, like cloning, represents a nontraditional reproductive technology that is not employed by any mammals.
We believe that the CRISPR/parthenogenesis methodologies used in the PNAS paper would be ethically unacceptable in humans for another reason. The authors of this paper did not provide details explaining how their technology will improve human infertility treatment or health care in the future. Their statement of impact is vague: “The success of parthenogenesis in mammals opens many opportunities in agriculture, research, and medicine.” Nontraditional reproductive technologies require a medical benefit in order to be ethically acceptable even before we address the definition of a human embryo.
It is important to emphasize that CRISPR technology, in itself, is ethically acceptable under the right conditions. CRISPR offers potentially transformative applications, including diagnosing human diseases, increasing longevity, eradicating viruses, enabling pig organs to be transplanted into humans, and treating many of the 7,000 genetic diseases that plague us. For example, Vertex Pharmaceuticals recently presented clinical data on a treatment for sickle cell disease or beta thalassemia that strengthen the case for pioneering CRISPR gene editing treatment. This treatment is predicted to cost dramatically less than the $1.7 million that health insurers spend to care for people with sickle cell disease over their lifetimes. Thus, these applications meet ethical standards of benefiting human health, and offering fairness and justice for all.
Similarly, several new reproductive technologies on the horizon merit continued funding and research because of their potential health benefits. For example, scientists have experimented with transplanting sperm-producing stem cells from infertile male mice to female mice to generate mouse puppies, and there are now several human clinical trials examining the safety and feasibility of approaches to use cryopreserved testicular stem cells to restore sperm production. This is an ethically justified technology that may have valuable applications to human health. For example, it could potentially be used by men undergoing treatment for testicular cancer in order to father children.
Since the days of Hippocrates, bioethics has offered a starting point for tackling the difficult dilemmas put forward by medicine. If scientists want to continue exploring parthenogenesis as a reproductive technology, they need to identify and present concrete explanations for how it will function ethically. They need to explain how the technology will improve human health, address human infertility, and offer affordable services that are beneficial to all. So far, they have not.