My first real memories of cloning came from a film by one of my favourite childhood bands S Club 7. In the film, Seeing Double, the band – as you can guess – are cloned by an ‘evil’ scientist (the classic scenario) who aims to take over the world with his army of famous clones. My fondness of the film is mostly due to the catchy songs and dance breaks – but in its simplistic nature it demonstrated the concept of cloning. In more recent years, I actually bumped into one of the members of the band in a club – to this day, I am not sure if it was the real person or their clone…
In general, I think most people consider cloning in the futuristic sense, whereby a clone of themselves is created to do all their work so they can sit on a beach somewhere and relax. Luckily for me, my clone already exists somewhere amongst the population of Victoria Secret models – or so I tell myself! But realistically, if it was possible to recreate a clone of me from my cells, then the clone would have to start from the beginning – from birth. And I don’t know about you, but having a baby version of me crawling about is not appealing.
Cloning can be an exciting area of research to not only imagine but to execute. However, along with cloning comes a whole heap of social, ethical and legal considerations that cannot be ignored. In this blog, we take a look at the history of cloning and the evolution of cloning techniques, as well as its perception in society and what the future may hold for cloning.
What is cloning?
The cloning process, in its simplest form, involves producing individuals or cells with identical DNA, either naturally or artificially. The monozygotic twin is considered the natural mammalian clone. In other words, they share almost identical DNA due to a single embryo splitting in two. However, as we very much know today, even two identical twins are not completely the same. Cloning, in fact, is a natural form of reproduction used by plants, fungi and bacteria that has enabled life forms to spread for hundreds of millions of years. In contrast, scientists have been able to tap into this process to artificially create clones. According to the NHGRI, there are three different types of artificial cloning:
- Gene cloning: This type involves creating copies of genes or DNA segments.
- Reproductive cloning: This type involves making duplicates of whole animals.
- Therapeutic cloning: This type involves creating embryonic stem cells.
To keep things simple and exciting, the focus of this blog will be on reproductive cloning, and its commercial applications.
The early days of reproductive cloning
The roots of cloning began in the nineteenth century. In 1885, German biologist Hans Driesch showed that blastomeres of two-cell sea urchin embryos could be physically separated and two entire embryos formed from each blastomere. This was the first-ever demonstration of artificial embryo twinning, the process of separating embryonic cells in the early stages of development. Each separated cell continues to grow and can be implanted into a surrogate.
Then, in 1902, German embryologist Hans Spemann used this same method to clone salamanders. Interestingly, the two cells of a salamander embryo are much stickier than sea urchin cells. Therefore, Spemann created a tiny noose from a strand of baby hair and tightened it between the cells until they separated. This experiment showed that this approach worked for a more complex animal – but only up to a certain stage of development.
Sticking with his noose and salamander, Spemann in 1928 essentially performed the first instance of nuclear transfer. At the 16-cell stage, Spemann used his noose to separate a cell from the rest of the embryo. This single cell grew into a new salamander embryo. This experiment demonstrated that the nucleus from an early embryonic cell could direct the complete growth of a salamander. In 1953, Robert Briggs and Thomas King (Figure 1) were able to perform the first successful nuclear transfer by transferring the nucleus from an early tadpole embryo into an enucleated frog egg. This led to the development of a tadpole.
In 1958, British biologist John Gurdon was the first to successfully clone an animal using somatic cell nuclear transfer. In this approach, the nucleus from a somatic cell is removed and placed into the enucleated egg cell of another animal. Gurdon transplanted the nucleus of a tadpole intestinal cell into an enucleated frog egg. He was able to create tadpoles that were genetically identical to one from which the intestinal cell was taken. This was one of the first major steps towards cloning.
Roslin Institute
Established in 1993, The Roslin Institute is an animal sciences research institute, part of the University of Edinburgh. In 1996, at the Institute, British scientists Ian Wilmut and Keith Campbell transferred the nuclei from cultured cells into enucleated sheep egg cells. All previous cloning experiments used donor nuclei from cells in early embryos. The lambs born from this experiment were named Megan and Morag and paved the way for Dolly. This experiment showed that cultured cells could supply donor nuclei and that it might be possible to use modified cells to create transgenic animals.
Then in 1996, in a landmark experiment, Wilmut and Campbell created the first mammal by somatic cell nuclear transfer. A nucleus from an adult sheep’s udder cells was transferred into an enucleated egg. Of the 277 attempts, only one produced an embryo that was carried to term in a surrogate mother. The famous lamb, named Dolly (after Dolly Parton), brought cloning to the forefront and into the public light (Figure 2). This experiment showed that differentiated cells, expressing only a distinct subset of genes, could be redesigned to grow an entirely new organism. This changed our understanding of a basic scientific principle. Now, despite not even being born when Dolly was made, like the rest of the world, the first thing I think of when someone says cloning is Dolly. Although Dolly died in 2003 when she was six years old, her legacy definitely lives on!
A life after dolly
After Dolly, the Roslin Institute carried on working with sheep, and in 1997 work was done to create the first mammals to be successfully cloned from cultured cells while also being transgenic. Polly and Molly produced Factor IX protein in their milk. The scientists achieved this by introducing the human Factor IX gene into the genome of sheep skin cells grown in the lab. They subsequently performed nuclear transfer using donor DNA from the cultured transgenic cells. The Factor IX gene encodes for a protein that helps with blood clotting and can be used to treat haemophilia. This experiment highlighted the potential medical and commercial uses for cloning.
Multiple other animals have been cloned since the experiments at Roslin, from mice to camels. Several endangered animals have also been cloned by somatic cell nuclear transfer, including the gaur (a type of ox) in 2001. The Macaque monkey in 2017 was the first successful cloning of a primate species using nuclear transfer.
What are the applications of cloning?
Apart from conducting these experiments to show that it was possible and to refine techniques, cloning also has several commercial applications. The initial hopes were to use cloning to produce animals that made human protein in the milk and blood of transgenic cloned animals. To date, several transgenic and cloned animals have been harvested in an experimental setting to produce different human proteins, including the human coagulation factor IX, human anti-thrombin and Alfa-1-antitrypsin. This approach, however, has been largely superseded by other more large-scale methods.
Another application of cloning is for the conservation of endangered species and de-extinction of extinct species. As mentioned, the gaur was the first endangered species cloned, but it died a few days after birth. The mouflon, a type of wild sheep, became the first clone of an endangered species that survived beyond infancy, surviving for at least 7 months after its birth. The first extinct species was cloned in 2009. The bucardo, a type of Spanish mountain goat, went extinct in 2000. The bucardo was cloned using goats as egg donors and surrogates yet died soon after birth. Many projects are currently being undertaken by Revive & Restore, who aim to enhance biodiversity through the genetic rescue of endangered and extinct species. One of their exciting projects is the Woolly Mammoth Revival Project (Figure 3), that aims to bring back this extinct species to re-populate tundra and forests in Eurasia and North America.
A final application is xenotransplantation, which is the transplantation of organs or cells from one species to another. Every day 17 people die waiting for an organ transplant. As of February 2021, there are over 107,000 people on the national transplant waiting list. Unfortunately, human-to-human transplantation is difficult due to scarcity of donor organs. Transgenic animals provide a potential solution to this problem. Pigs currently appear to be the most suitable donor animal, due to their similar organ sizes. Their maintenance is also relatively cheap. However, one of the biggest problems associated with xenotransplantation is that the immune system of the human recipient attacks the transplanted organ, leading to transplant rejection.
In popular culture
Cloning in popular culture is often depicted as something negative. From bringing back dinosaurs using DNA extracted from fossils, to cloning human counterparts for organ donations, science fiction films have used the concept of cloning to emphasise the dangers associated with such scientific developments. With everything in popular culture, these portrayals reflect societal fears and questions surrounding advanced technology. The news of Dolly the sheep and its widespread media attention, captivated the world and made many people question – what if we could clone humans? Conversations about human cloning often relate to fears of eugenics and loss of human individuality. Cloning itself is complex, bringing both potential benefits and negative consequences. I think it is important to note that cloning, in its current form, is not this futuristic idea of creating new human beings. Current research in fact has potential therapeutic applications and can help save endangered species. Nonetheless, it is important that we acknowledge these fears in society and identify where they originate from. Uneasiness around new scientific technologies that can ultimately change the way we live is expected and should not be ignored. Instead, recognition of these relationships makes it possible for those involved in social, ethical and legal discourse to approach these topics more sensitively and effectively.
The future
Will the future be full of cloned famous musicians, woolly mammoths and dinosaurs roaming the streets? I highly doubt it. But then again, never say never. Would I want that world? Probably not. Even if we could clone ourselves, contrary to what people think, your clone would not be you. Firstly, as mentioned before, your clone would be a baby. Secondly, environmental and several important biological processes, would ultimately result in a human being that is most likely nothing like you. Misinformation surrounding cloning is profound. The fact that most people (including myself) only know about Dolly the Sheep in regard to cloning shows how little our mindsets have progressed in the past twenty years. Even writing this, I struggled to find research and news that addressed modern-day cloning. If we are to use cloning as a method to advance human health and disease, we must first address the fears surrounding cloning. We must create a new narrative, with clear transparency and discussion surrounding the applications and challenges of cloning. I think it’s time Dolly gracefully retired from her 9 to 5 job as the face of cloning and made way for the next cloning superstar!
Check out our interview with Bill Ritchie the embryologist behind Dolly the Sheep. Now retired, Bill takes a look back at the path that led to Dolly, her legacy and the future of the cloning field.
References
- Maio G. Cloning in the media and popular culture: An analysis of German documentaries reveals beliefs and prejudices that are common elsewhere. EMBO reports. 2006 Mar;7(3):241-5.
- Franjić S. Ethical Debates about Cloning. Asploro Journal of Biomedical and Clinical Case Reports. 2019;2019(3):93.
- Tadesse T, Muluneh T and Abraham S. Agricultural and Biomedical Application of Animal Cloning: Review. Journal of Natural Sciences Research. 2018;8(3).
- McKinnell RG, Di Berardino MA. The biology of cloning: history and rationale. BioScience. 1999 Nov 1;49(11):875-85.
