Two Decades After Dolly, Mammalian Cloning Closes in on Humans
She would have turned 20 last July. She died in 2003 in the same place where she was born—Edinburgh, Scotland. Oddly, she had three mothers and no father. Yet her birth announcement rocked the world. As you may have guessed, I'm referring to Dolly the sheep, who was the first mammal cloned from an adult.
Dolly's birth, on July 5, 1996, caught everyone by surprise when it was announced months later. At the time, most scientists predicted it would be at least 15 to 20 years before the first mammal was cloned.1 There had been little serious discussion of cloning in the scientific communities, though ethicists had raised some concerns. But every time they brought up the horrifying question of human cloning, scientists would pooh-pooh the idea, perhaps out of fear of a public anti-science backlash.2 Even Hollywood was caught flat-footed, with current events upending the production schedule and futuristic plot of The Sixth Day, a film about human cloning.
Earlier successes with intermediate steps toward mammalian cloning had been virtually ignored, because the work was not conducted in a "hot" area or at a prestigious research institution. But when the news of a cloned sheep spread, alarm bells went off in all quarters, and reporters flocked to the unassuming Roslin Institute, where Dolly was born. Politicians, scientists, and ethicists reacted with varying degrees of alarm or anticipation.
The Original Purpose
The original impetus behind cloning-related research was the desire for a reliable source of drugs. Researchers had already succeeded in inserting protein-producing genes into embryos of animals such as chickens and sheep, and extracting the drug from the eggs or milk of the adult clones. If the animals could be cloned, every batch would be of consistent quality. Keith Campbell and Ian Wilmut, heads of the research team that created Dolly, were pursuing this possibility. They had no interest in cloning humans, or even in cloning animals per se. But once Dolly was born, it was inevitable that the connection between cloning a non-human mammal and the prospect of cloning humans would be made, and the technological distance to be traversed was imagined to be alarmingly short.
History has proved otherwise.
Humans are not just mammals, but a particular kind of mammal: primates. Unique characteristics of primate eggs, combined with their sensitivity to ultraviolet light and to certain dyes, make the cloning process technically impracticable.3 Several ambitious researchers have claimed to have cloned human beings, but none, including the disgraced Hwang Woo Suk, have offered verifiable proof.
Cloning is still used for its original purpose—to produce human antibodies or blood-clotting drugs in the milk of sheep and cows. Clones are also used to test new drugs. Since they are genetically identical, each clone should respond to the drug in the same way. And although not a medical concern, cloning has been suggested as a way to preserve endangered species. Jurassic World, anyone?
Cloning techniques have also improved. Dolly was the sole survivor of 270 attempts, an efficiency rate of 0.3 percent. Current efficiency rates among animals have improved to three percent,4 but that still requires an inordinate number of eggs. (In the original process called "somatic cell nuclear transfer," the egg nucleus is removed, and replaced with the nucleus from the adult animal to be cloned. Each attempt requires a fresh egg.)
Of course, at the time of Dolly's birth, future prospects could not be accurately predicted. Justifiably, the ethical conversation centered on profound questions of human identity, procreation versus production of children, mortality, and hubris. Science could no longer claim neutrality in matters of deep moral relevance. Theoretical improbabilities or scientific indifference were not reliable barriers against morally suspect research.
Disapprobation of human cloning was nearly universal at first. But the promise of finding new cures, eliminating genetic diseases, testing drugs for serious ailments, or solving the problems of infertility proved just too tantalizing to resist. As a result, human cloning was conveniently divided into two purportedly distinct categories: "therapeutic" and "reproductive." Reproductive cloning, a linguistic tautology, means to clone and implant an embryo with the intent to gestate and give birth. Therapeutic or research cloning, more properly labeled "experimental cloning," confines cloned embryos to the lab, to be subjected to various lethal experiments and, in all cases, destroyed before reaching 14 days old. The relevant question for all cloned embryos, then, is their intended fate: as a desired child, or as research material.
The story of Dolly's impact is a cautionary tale. Twenty years ago, bioethicists vigorously rejected the premise of human cloning. In the U.S., a funding ban and moratorium on research were proposed. The United Nations banned reproductive cloning in 2001.
But despite initial horror at all forms of human cloning, resistance to experimental cloning has weakened. Barely five years after Dolly's birth, the UK approved experimental cloning of human beings, and other nations have followed suit. Similarly, moral concerns about tinkering with the human embryo in other contexts are evaporating. Human embryos are subjected to CRISPR, a technique intended to replace defective genes with healthy ones. So far, the technique has a low efficiency rate, and, of course, all the embryos ultimately die. Another effort to correct a problem gene is the "3-parent embryo," where one of several techniques is employed to remove the nucleus from an egg with healthy mitochondrial DNA (mtDNA), and use it to replace the nucleus of an embryo created by a father and a mother who has unhealthy mtDNA. Some of the embryos created this way are showing problems, with undesired mtDNA being introduced into the new embryo and overwhelming the healthy mtDNA.5
Technological success has a funny way of erasing "black lines." When researchers announced success in coaxing human embryos to survive for 13 days, the "14-day rule" was questioned. The nearly universal rule bans growing embryos past 14 days, the point when twinning is no longer possible. Now, the rule is being re-evaluated on the grounds of its being a barrier to research that could "benefit humankind."
Human cloning is only the most notorious of the reproductive and genetic technologies. Our initial, and proper, aversion to making full-size copies of people has endured, perhaps because, so far, no cute babies have been produced. Meanwhile, subtler technologies that inure us to the harms of massive experimentation on and destruction of embryonic human beings develop apace. Initial bans evolve into moratoria, followed by proposed research and funding guidelines open to obligatory public comment, then issued despite protests from right-thinking citizens, including ethicists. Without an iconic figure like Dolly to jar us awake, scientists, ethicists, politicians, and the public have been lulled into moral somnolence, swaddled by reveries of a perfected future of disease-free children and pain-free existence. It is better to dream of a world where research and ethics work hand in glove with solicitude for the embryo, and for the benefit of all. •Paige Comstock Cunningham
is the Executive Director of The Center for Bioethics & Human Dignity in Deerfield, Illinois.This article originally appeared in Salvo, Issue #39, Winter 2018 Copyright © 2019 Salvo | www.salvomag.com https://salvomag.com/article/salvo39/sheep-astray