On 5 July 1996, on a soft summer night in Rosslyn, Scotland, one of the most famous sheep in history was quietly born in a barn near the Rosslyn Institute. She was born without as much attention, without the media spotlight, and even her main creator, Ian Wilmut, knew nothing about the moment. It was not until February of the following year that the existence of this small animal was made public.
A sheep destined to go to history | Paul Hudson / Wikimedia Commons
This pale gray-white critter looks no different from the thousands of lambs in the Scottish hills, but her peculiarity soon sparked a worldwide debate — she was the first mammal to be successfully cloned by somatic cells, a complete organism developed from the mammary nucleus of an adult ewe. Ian Wilmut named the lamb "Dolly Parton" after the American country singer Dolly Parton.
The first cloned sheep
"clone" is derived from the Greek word "κλών" (klōn, young branches), which refers to the process of cultivating new plants from cuttings of young branches of plants. We talked about the totipotency of cells in high school biology books, and it is relatively easy to induce plant somatic cell differentiation and development, and there are many vegetative organs of plants that do not even need any induction to become new strains. In the long history of agricultural production, human beings have explored many methods of asexual reproduction of plants, and naturally they have also thought about whether they can use the same method to mass-produce animals with excellent traits.
Plant cloning is easy to achieve, and Utah has a world record for "the world's largest monolithic organism", which is a cloned tremlin that sprouts through the roots and grows naturally | Scott Catron / Wikimedia Commons
But biology books also tell us that it's much harder to restore the totipotency of animal cells. Prior to Dolly, there had been attempts to clone animals with some success. Back in 1952, Robert Briggs and Thomas B. Robert Briggs and Thomas J. King cloned the northern leopard frog; in 1963, Tong Di Zhou cloned carp. How can advances in biological technology be less zebrafish? So in 1981, zebrafish were also cloned.
Gradually, there is hope that cloning techniques will be applied to more complex animals. In the decade or so before Dolly was born, both sheep and mice had been successfully cloned—albeit using early embryonic cells rather than somatic cells (which sounds more like an assisted reproductive technique than replication). Obviously, nuclear transplant cloning is easier to achieve on inferior (or more primitive) animals and cells with low degree of differentiation, which also highlights the significance of Dolly, as mentioned above, this is the first successful use of somatic nuclei to complete mammalian cloning.
Doley's birth, remember the middle school textbooks? | Squidonius / Wikimedia Commons
Her nuclear donor was a Finnish-Dorset sheep, and the egg donor was a Scottish black-faced sheep, and it was clear that Dolly's traits should be determined by the nucleus, and she was, of course, a Finnish-Dorset sheep.
Is cloning a dangerous technique?
The process of cloning Dolly is not very smooth, there are a total of 277 test eggs at the same time as Dolly, only 13 of them develop into embryos, and after the embryo is transferred, only Dolly is born alone. The success ratio is 1:13:277, which shows that in the 1990s, somatic cell transplant cloning was still a very immature technology, but this did not prevent people from heated discussion and prospects.
Looking back on the twentieth century, many advances in the field of biomedicine have greatly changed human lifestyles and social forms, such as the discovery of penicillin, the discovery of genetic structure, the elimination of smallpox, and so on. The birth of Dolly is also one of them, but unlike the previous ones, dolly's birth has promoted human awareness of its own meaning.
Blade Runner 2049 tells the story of a clone who is a slave and a human who slaughters clones | Brecht Bug / Flickr
To exaggerate, the definition of "human" has changed since the moment Dolly was made public, and if it is possible to escape from the excuse of technological gaps before this, then human beings now have to face this problem:
"Will humans clone humans?"
Before Dolly was born, human cloning was more of a science fiction theme, or as a technical possibility (like Blade Runner), which many considered to be something that was hopelessly achieved in the near future. However, with the advent of Dolly, society's view of cloning technology has plummeted, and some even believe that the development of science has touched the brink of destruction of human beings. In literary and artistic creation, the time-honored science fiction theme of "cloning" has once again shined, and films such as "The Sixth Day", "Escape from Clone Island" and "Moon" are the reflections of this trend of thought.
It's not impossible to clone people today| Medspace / Wikimedia Commons
However, artistic creation is only artistic creation. At least for now, human cloning is not in any researcher's plan and lacks a material basis. The significance of fully replicated animal cloning is rather limited, and it has been recognized that one of the essences of species conservation is the conservation of genetic diversity, and it is meaningless to simply increase the number of individuals. In 1998, a domestic scientific research team set up a project to use xenonuclear cloning (the giant panda body nucleus into other animals to denuclear oocytes) to breed giant pandas, the project initially made some progress, and then, the embryo synthesis failure rate remained high, coupled with the change in the concept of protection, and finally the idea of "saving species with cloning" was rejected.
Dolly was born old?
What's more, life is a complex system produced in the process of interacting with the environment, and people are the sum of social relations, and the army of cloned pandas or clones can only be science fiction for the time being. The more realistic implications of Clondoli should lie in the possibilities of medical research, such as targeted cloning of organs, replication of genetically engineered animals, and even induction of self-regeneration in the human body. Just a few years after Dolly's birth, the organ cloning and culture research initiated by the biomedical company mushroomed, bearing in mind that at that time, human self-understanding was far less clear than today, and the human genome project would not be completed until almost a decade later.
Jurassic Park presents an imaginary | of resurrecting extinct animals Frank Vincentz / Wikimedia Commons
Still, the cloning craze seems to have been poured cold water very quickly. Today, 2003 (February 14), Dolly, at the age of six and a half, died at the Rosslyn Institute, not living to the average life expectancy of a sheep— eleven to twelve— caused by lung disease and arthritis. At the time, the prevailing view was that Dolly was born at a genetic age of six, the same as a nuclear donor.
In fact, at the time of Dolly's birth, some people had issued similar concerns, and the telomere mechanism discovered earlier in the twentieth century seemed to secretly determine the fate of Dolly's premature aging. Telomeres are thalers that are the base sequences of TTAGGG, repeat 500 to 3000 times, and bind to some proteins (this is to say that the telomeres of mammals, telomere sequences and repeats of other biological taxa are different). Each time the genetic material splits, the telomeres shorten by one segment to protect the chromosomes themselves from damage.
Simply put, telomeres are like something wrapped around the ends of a shoelace, and every time a chromosome is copied, it wears down some | Ultrabem / Wikimedia Commons
Telomeres in primitive state stem cells are the longest, and when telomeres are shortened to none, cell division damages the chromosome itself, leading to cell death. In some cells, such as egg cells, there are enzymes that lengthen telomeres, which are generally lacking in somatic cells. Opponents of the "cloned sheep premature aging" view believe that since egg cells have their own telomerase, they may use some mechanism to prolong somatic cells that are too short telomeres.
The future of cloning technology
Reality seems to be on the side of pessimists, and a 1999 study showed that Dolly's telomeres were indeed shorter, suggesting that Dolly may have experienced excessive aging and that it seemed as if somatic cell cloning was about to pass. But follow-up reports raised objections, with the Roslin Institute saying it had found no signs of premature aging in Dolly, whose poor health may have been due to lung lesions caused by long-term indoor life.
The 2016 new study went a step further, reporting that 13 cloned sheep lived healthily to the age of eight, four of them from dolly's same cell line. No evidence of senescent diseases was found in them, which basically ruled out the adverse effects of somatic cell cloning, and also showed that Dolly's premature death was likely accidental in the experimental process.
Dolly's cause of death was not | cellular senescence Sgerbic / Wikimedia Commons
This is undoubtedly good news in the biomedical field, but the current research direction is mainly focused on induced stem cell technology (iPScell), that is, the use of inducible factors to dedifferentiate mature somatic cells and return to the stem cell state. Today's iPScell technology is developing rapidly and has been widely used, but it has also produced many scientific frauds.
To this day, people have not fully sorted out the mechanisms behind somatic cell cloning of animals, and Dolly and her successors have brought us more and more mechanisms to explore and moral and ethical issues that need to be identified. Although complete human cloning will not be allowed, in the future, related derivative technologies may still be used to transform humans themselves, or even redefine human beings.
But that's what we and the lamb can't understand.
This article is from the species calendar, welcome to forward
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