From Dolly to Zhong Zhong to Human Cloning?

Feature Article From Dolly to Zhong Zhong to Human Cloning? Zhong Zhong and Hua Hua (Photo courtesy: www.engadget.com) Biju Dharmapalan formal and ancient name for “China.” This scientific milestone has political HE recent news about the overtones. The name has been selected successful cloning of monkeys to show the Chinese supremacy in the by Chinese scientists grabbed scientific world, where most of the T dolly.roslin.ed.ac.uk) media attention some time back. In countries have put a blanket ban on a research paper published in the human cloning research. journal Cell (February 8, 2018), Public attention in cloning got

scientists from the Chinese Academy significance with the birth of Dolly ( Photo courtesy: of Sciences in Shanghai announced the in 1996 by Sir Ian Wilmut’s group at successful cloning of a pair of Long- the Scottish Centre for Regenerative tailed macaques Zhong Zhong and Hua Medicine at the University of Edinburgh Dolly and her surrogate mother Hua using DNA from foetal connective through a technique known as Somatic tissue cells, using Somatic Cell Nuclear Cell Nuclear Transfer (SCNT). In then merges with the implanted nucleus Transfer (SCNT) technique, which was SCNT, the nucleus is removed from and develops into a clone of whatever it used to clone Dolly. an egg cell and is replaced with a was that donated the nucleus. The name Zhong Zhong was different nucleus from another cell, Dolly was cloned from a cell taken derived from the term Zhonghua, a usually a somatic cell. The egg cell from the mammary gland of a six-year-

TIMELINE OF ANIMAL CLONING

1894: German biologist Hans Driesch used Xenopus laevis to show Schatten creates Tetra, a rhesus takes a two-cell sea urchin from that nuclei from specialised cells macaque, using embryo splitting the Bay of Naples and shakes still held the potential to be any technique. The cells in the it in a beaker of water. The cells cell despite their specialisation. embryo are split after reaching part, giving rise to two identical 1963: Chinese embryologist Tong the eight-celled stage to create sea urchins. Dizhou applied the same four identical two-celled embryos. 1902: German scientist Hans Spemann technique in fish. 2000: Oregon researchers created the uses a fine hair from his baby 1996: British embryologist Sir Ian first genetically modified monkey, son to split a salamander embryo Wilmut clones Dolly the sheep ANDi. It was engineered to carry into two. using a technique called somatic a gene from another species. 1952: American scientists Robert cell nuclear transfer, in which the The work demonstrates that a Briggs and Thomas King perform DNA from one animal is placed foreign gene can be delivered a successful nuclear transfer, into an empty donor egg. The and inserted into a primate by moving a nucleus from an two components are stimulated chromosome. embryonic frog cell into an egg with an electric current and given 2001: The first attempt at using cloning cell whose own nucleus had nutrients that stimulate them to to boost an endangered species been removed. grow into an embryo. fails after a cloned bison called 1962: Oxford biologist John Gurdon 1999: A team led by Prof. Gerald Noah dies soon after birth.

40 | Science Reporter | August 2018 Illustration courtesy: www.newscientist.com

old Finn Dorset sheep and an egg cell with the other sheep at the Institute. including humans. It also initiated taken from a Scottish Blackface sheep. Over the years Dolly had a total of serious discussions on ethical issues She was born to her Scottish Blackface six lambs with a Welsh Mountain ram unheard of till then. surrogate mother on 5 July 1996. called David. Their first lamb, Bonnie, Earlier, scientists had successfully Dolly’s white face was one of the was born in April 1998, twins Sally used this technique to produce clones first signs that she was a clone because and Rosie were born the following year from sheep, mice, cows, dogs, etc. if she was genetically related to her and triplets Lucy, Darcy and Cotton In 1999, a “cloned” rhesus monkey surrogate mother, she would have had the year after. named Tetra was born, but she was a black face. Because Dolly’s DNA Dolly was euthanised on 14 created through a less sophisticated came from a mammary gland cell, she February 2003, at the age of six, after method called embryo splitting or was named after the country singer she developed serious health issues. artificial twinning. Although it mimics Dolly Parton. Dolly was important After her death, Dolly’s body is placed the natural process through which because she was the first mammal to be in the National Museum of Scotland at twins are born, embryo splitting can cloned from an adult cell. Edinburgh as a historical specimen. only create four offspring at a time, Dolly spent her life at The Roslin The birth of Dolly evinced interest limiting its usefulness. Institute and, apart from the occasional among the scientific community to The latest breakthrough through media appearance, led a normal life clone other potentially useful animals Zhong Zhong and Hua Hua allows for a near limitless production of clones. SCNT has proven to be difficult in primates until this news was broken by 2001: Researchers from Texas A&M found to have been fraudulent. the Chinese team. University create the first cloned 2013: Embryonic stem cells are Twenty-three species, including cat called “Cc”, short for “carbon extracted from cloned human rats, cats, dogs, and cows have all copy”. embryos by Shoukhrat Mitalipov been created, but primate cells proved 2004: The first cloned monkey embryos at the Oregon Regional Primate resistant. In 2003, scientists from the are created using the Dolly Research Center. University of Pittsburg tried using 716 technique, but none survive long eggs but failed to create even a single 2016: Mu-ming Poo at the Institute enough to be implanted. clone, it was suggested that primate of Neuroscience in Shanghai, cloning is impossible by this method. 2004: South Korean scientist, Woo Suk China, unveils the world’s first Hwang, claims to have obtained genetically engineered monkey The Chinese scientists got 192 embryonic stem cells from cloned with a version of Parkinson’s embryos from 290 tries, with 22 human embryos. disease. pregnancies and two monkeys born alive; both died within hours. Using 2005: Snuppy, the world’s first cloned 2018: The world’s first cloned monkeys dog is unveiled, also by Woo Suk using the Dolly technique are cells from fetuses, they got 109 embryos Hwang. unveiled in China. They are from 137 tries, six pregnancies, and 2006: Woo Suk Hwang’s claims of called Zhong Zhong and Hua two live births – both females and, cloning human embryos are Hua. since they came from cells of the same monkey, identical twins.

August 2018 | Science Reporter | 41 Henry Greely wrote in his book The End of Sex and the Future of Human Reproduction: “Within twenty, maybe forty years most people in developed countries will stop having sex for the purpose of reproduction.”

The success of the Shanghai team (Photo courtesy: www.sundaypost.com) became possible primarily due to two chemicals they used – trichostatin A and Dolly as a historical specimen in the National Museum of Scotland at Edinburgh Kdm4d. Together they reprogrammed the biology of human diseases and later found to be a scientific fraud. the donor DNA, awakening genes needed development of treatments for diseases to produce an entire organism. That In 2016, Japanese scientists like Alzheimer’s, Parkinson’s, and increased the percentage of SCNT eggs produced egg from the skin cells of cancer. For example, all the recent mice through a process called In- that developed into embryos, and also Alzheimer’s medications that looked Vitro Gametogenesis (IVG). Similarly improved the embryos’ quality, making promising in mouse models haven’t been scientists like Shoukhrat Mitalipov of them more like naturally fertilised eggs. effective in our species. Macaques, being Oregon Health and Science University However, the efficiency was still very much closer to us, could give a better successfully edited human embryos low and they couldn’t achieve success indication as to whether or not new drugs through gene-editing technique CRISPR using adult cells. would be effective in humans. making designer babies a reality. Monkeys have many similarities The successful cloning of Zhong with humans both genetically and Zhong and Hua Hua has renewed interest The birth of Zhong Zhong and physiologically. This makes them better in human cloning too. Scientists have Hua Hua has opened up discussions laboratory model animals compared been trying to make human clones but on the ethics of human cloning. Many to other animals like rats or mice, to so far have been unsuccessful, except the mainstream scientists and religious understand human problems properly. report in 2006 by Woo Suk who claimed leaders across the globe have approached It would be useful in understanding successful cloning of humans, but was human cloning with caution. But it also holds out hope for couples who don’t have babies due to health issues or for same-sex couples. Henry Greely wrote in his book The End of Sex and the Future of Human Reproduction: “Within twenty, maybe forty years most people in developed countries will stop having sex for the purpose of reproduction.” Who knows in future we may have human clones in laboratory cages as experimental animals, similar to present (Photo credit: www.news.cn) day poor mice!

Mr Biju Dharmapalan is Assistant Professor & Head of Department, School of Biosciences, Mar Athanasios College For Advanced Studies (MACFAST), Tiruvalla-689101, Muming Poo, Sun Qiang and Liu Zhen, the lead researchers, addressing a press conference Kerala; Email: [email protected]/biju_ [email protected]

42 | Science Reporter | August 2018