Sheep Astray: Two Decades After Dolly, Mammalian Cloning Closes in on Humans

Editors Note: This article appeared in Salvo 39, Winter 2016 edition and is used by permission.

She would have turned 20 last July. She died in 2003 in the same place where she was born in 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 caught everyone by surprise when it was announced months later. At the time, most scientists predicted it would be at least 15-20 years before the first mammal would be cloned.[1] There had been little serious discussion in the scientific communities, but ethicists had raised some concerns. From the early years of bioethics, every time the ethicists brought up the horrifying question of human cloning, scientists would pooh-pooh the idea, concerned about 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 to mammalian cloning were virtually ignored, because the work was not being conducted in a “hot” area, or at a prestigious research institution. But, when news of the cloned sheep spread, alarm bells went off in all quarters, and reporters flocked to the unassuming Roslin Institute where Dolly was born. Politics, scientists, and ethicists reacted in varying degrees of alarm or anticipation.

The original impetus for 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 cloning animals per se. But once Dolly was born, the connection between cloning a non-human mammal and the prospect of cloning humans was inevitable, 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 sensitivity to ultraviolet light and dyes used the in process, make the process technically impenetrable.[3] Several ambitious researchers have claimed to clone human beings, but none, including the disgraced researcher Hwang Woo Suk, have offered verifiable proof.

Cloning for medical purposes is presently used for the 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 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 are at three percent,[4] an improvement, but one which 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.)

At the time, of course, 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. However, the tantalizing promises of finding new cures, eliminating genetic diseases, testing drugs for serious ailments, or solving the problems of infertility were just too appetizing to resist. As a result human cloning was conveniently divided into two purportedly distinct categories: ‘therapeutic’ and ‘reproductive.’ Reproductive cloning, a linguistic tautology, means the cloning and implanting of 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 they reach 14 days. The relevant question for all cloned embryos 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 US, a funding ban and moratorium on research were proposed. The United Nations banned reproductive cloning in 2001.

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,” in which one of several techniques is employed to remove the nucleus from an egg with healthy mitochondrial DNA (mtDNA), and replace it with the nucleus from 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 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 13 days, the “14-day rule” was raised. The nearly universal rule bans growing embryos past 14 days, when twinning is no longer possible. Now, the rule is questioned as a barrier to research that could “benefit humankind.”

Human cloning is but 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 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 protest 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.

 

Reference


[1] Robin McKie, “Where Dolly Went Astray.” The Guardian (Feb. 18, 2007): https://www.theguardian.com/science/2007/feb/18/health.healthandwellbeing

[2] See, e.g., Gina Kolata, Clone: The Road to Dolly and the Path Ahead (New York: William Morrow, 1998).

[3] “Cloning Fact Sheet.” National Human Genome Research Institute, National Institutes of Health. https://www.genome.gov/25020028/cloning-fact-sheet/

[4] McKie.

[5] Kellly Servick, “Why ‘Three-parent’ Embryo Procedure Could Fail,” Science (May 19, 2016):  http://www.sciencemag.org/news/2016/05/why-three-parent-embryo-procedure-could-fail

 

Creative Commons License