First animal clone and its implications

Identification: First mammal successfully cloned from adult cells

Dates: Born July 5, 1996; died February 14, 2003

The birth of Dolly and subsequently cloned animals raised a host of ethical issues and opened the door to possible means of improving human health and the environment. Dolly’s comparatively short life span, about half that of the typical sheep of her breed, may have been related to her clone origins.

On February 5, 1997, Ian Wilmut of the Roslin Institute in Edinburgh, Scotland, announced the birth of Dolly the sheep, the first clone produced from a cell taken from an adult mammal. Scientists and the general public were shocked at this announcement, because it was believed that cloning a mammal from an adult cell was, at the time, technically impossible. Dolly was seven months old before her birth was made public. Because she was cloned from mammary cells, the research team named her after well-endowed country-western singer Dolly Parton.

How Dolly Was Created

A clone is an organism developed from a single cell isolated from another organism. The cell donor and the clone are genetically identical. Prior to the creation of Dolly, no attempts at cloning a mammal from adult cells had been unequivocally successful. In the early 1980s, scientists had created clones of mammals by using donor cells from young embryos. The research team that cloned Dolly first cloned a pair of sheep, Megan and Morag, from embryonic cells grown in the laboratory. Adult cells and embryonic cells have identical genetic material, or deoxyribonucleic acid (DNA); however, adult cells produce proteins specific to the type of cell they become. For example, brain cells produce neurotransmitters and do not produce hemoglobin, even though they possess the hemoglobin gene. Scientists believed that the structure of the DNA in an adult cell was irreversibly altered during the process of maturation to gain this specificity and therefore could not be used to produce a clone.

Wilmut and his colleagues at the Roslin Institute used a novel approach to clone Dolly. The donor cells were sheep udder cells from a six-year-old pregnant ewe. The cells had been frozen for about three years, and the donor was long deceased. The researchers believed that prior attempts at cloning mammals from adult cells had failed because the cells were too active or in the wrong phase of their life. To make the cells quiescent, the research team starved them for several days. Meanwhile, the researchers removed genetic material of eggs from a different breed of sheep, a process called enucleation. They then fused the starved cells with the enucleated donor eggs and implanted them into surrogate mother sheep of a third breed. Of 277 attempts, only a single egg went full-term, resulting in the birth of Dolly. Dolly looked strikingly different from the breed of the egg donor or the surrogate mother but identical to the breed that donated the adult DNA, an observation that provides suggestive evidence that she developed from the donor DNA.

Initially many questions surrounded the validity of the experiment that produced Dolly. Some scientists believed that she could have been the result of a contaminating fetal cell, and the results of the experiment were not easily replicated by other researchers. However, in July, 1998, Japanese scientists announced the birth of two calves cloned from adult cow uterus cells, and researchers in Hawaii successfully produced more than fifty mouse clones from adult mouse ovarian cells. Also, DNA analysis of Dolly confirmed that she was indeed the first clone of an adult mammal. After reaching sexual maturity, Dolly mated naturally and on April 13, 1998, gave birth to a lamb, showing that she was a healthy young adult whose ability to reproduce was not compromised by her unusual origin. She would have two more pregnancies and bear five more lambs during her life.

Implications

In May, 1999, researchers found that the telomeres in Dolly’s cells were shorter than those in other mammals of similar age, a finding borne out in other cloning research. Telomeres, which are sequences at the ends of chromosomes, become progressively shorter as an organism ages, but it was not clear whether Dolly’s life span would be shorter than usual.

Dolly contracted a lung disease and was euthanized in February 2003, at the age of six and a half. Sheep of her breed typically live to be about twelve. A postmortem examination confirmed that her lung ailment was sheep pulmonary adenomatosis (a lung tumor associated with a retrovirus), a fatal disease common in older sheep, particularly those living indoors. The examination revealed no other abnormalities. During her lifetime, she had tended toward stoutness, but her keepers attributed Dolly’s weight problem not to her clone origins but to her living mostly indoors and being fed treats by her many visitors. Dolly’s remains were donated to the National Museum of Scotland in Edinburgh, where her preserved body was placed on exhibit.

Dolly was diagnosed with osteoarthritis in the left knee at the age of five and a half, leading to a widespread misconception that Dolly had developed osteoarthritis prematurely compared to naturally conceived sheep. However, in 2017 researchers from the University of Nottingham and the University of Glasgow examined radiographs of the skeletons of Dolly, her daughter Bonnie, and two other sheep who were cloned at the same time as Dolly and found that none of the four exhibited osteoarthritis more advanced than was usual for naturally conceived sheep of the same age. (The majority of sheep develop the disease over the course of their lives.) In addition, four sheep who were cloned from the same progenitor as Dolly were examined when they were nine years old and were found to have arthritis that was in fact less severe than that of the typical naturally conceived sheep of that age.

There are numerous potential applications for the cloning technology that produced Dolly. Scientists envision using cloning in tandem with genetic engineering to benefit medicine and create animals with organs suitable for transplant into humans or ones that produce human proteins for use in pharmaceuticals. In fact, Wilmut’s research was sponsored by the Scottish pharmaceutical company PPL Therapeutics, Ltd. His subsequent research involved sheep cloned from fetal cells that had been genetically altered to carry a human gene that caused the animals’ milk to contain a blood-clotting protein with the potential for use in treating human hemophilia. In early 2014 it was reported that as much as five hundred pigs per year were being cloned in China by the Beijing Genomics Institute in order to test new medicines.

Some researchers envision entire herds of genetically identical cattle. Because it is very difficult to produce prize milk- or meat-producing animals consistently with traditional breeding methods, repeated cloning of one prize breeding animal would greatly speed the process. A potentially serious problem with genetically identical herds, however, is that genetic diversity allows species to survive changes in their environment and attacks by disease. Diseases affecting only a few individuals of a genetically diverse species may become rampant in a genetically identical one. If genetic diversity is lost, it could lead to endangering the species or perhaps even the extinction of that species.

Cloning has long been regarded as a possible means of bringing endangered animal species back from the brink of extinction, particularly those species that do not breed well in captivity. However, the expense and failure rate of the technique may be too great for it to be practicable. The year 2001 saw the birth of the world’s first cloned endangered wild animals. A cloned gaur (a type of Southeast Asian ox) was successfully brought to term by a domestic cow that served as its surrogate mother, but the newborn succumbed to common dysentery two days after its birth. A cloned European mouflon, one of the world’s smallest wild sheep species, fared better. Born to a domestic sheep, the mouflon was raised at a wildlife center in Sardinia, Italy. Other endangered species that have since been successfully cloned include the Javan banteng (a type of wild cattle) and the African wildcat. The first clone of an extinct animal was born in 2009. Cloned from the frozen skin of a bucardo, or Pyrenean ibex, a subspecies of wild goat that went extinct in 2000, the animal died minutes after birth.

Bibliography

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"Radiographs of Dolly's Skeleton Show No Signs of Abnormal Osteoarthritis." ScienceDaily, 23 Nov. 2017, www.sciencedaily.com/releases/2017/11/171123095146.htm. Accessed 5 Dec. 2017.

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