It seems that every week, newspapers report on new advances in the science of cloning. Everybody knows about Dolly the cloned sheep, but few people know all the details about cloning, including the fact that scientists have been working on it for over 100 years.
Cloning in Nature
Cloning has been going on in the natural world for thousands of years. A clone is simply one living thing made from another, leading to two organisms with the same set of genes. In that sense, identical twins are clones, because they have identical DNA. Sometimes, plants are self-pollinated, producing seeds and eventually more plants with the same genetic code. Some forests are made entirely of trees originating from one single plant; the original tree spread its roots, which later sprouted new trees. When earthworms are cut in half, they regenerate the missing parts of their bodies, leading to two worms with the same set of genes. However, the ability to intentionally create a clone in the animal kingdom by working on the cellular level is a very recent development.
The first cloned animals were created by Hans Dreisch in the late 1800's. Dreich's original goal was not to create identical animals, but to prove that genetic material is not lost during cell division. Dreich's experiments involved sea urchins, which he picked because they have large embryo cells, and grow independently of their mothers. Dreich took a 2 celled embryo of a sea urchin and shook it in a beaker full of sea water until the two cells separated. Each grew independently, and formed a separate, whole sea urchin.
In 1902, another scientist, embryologist Hans Spemman, used a hair from his infant son as a knife to separate a 2-celled embryo of a salamander, which also grow externally. He later separated a single cell from a 16-celled embryo. In these experiments, both the large and the small embryos developed into identical adult salamanders. Spemman went on to propose what he called a "fantastical experiment" -- to remove the genetic material from an adult cell, and use it to grow another adult. In this way, he theorized, he would be able to prove that no genetic material was lost as cells grew and divided.
There were no major advances in cloning until November of 1951, when a team of scientists in Philadelphia working at the lab of Robert Briggs cloned a frog embryo. This team did not simply break off a cell from an embryo, however. They took the nucleus out of a frog embryo cell and used it to replace the nucleus of an unfertilized frog egg cell, completing the "fantastical experiment" of nearly 50 years before. Once the egg cell detected that it had a full set of chromosomes, it began to divide and grow. This was the first time that this process, called nuclear transplant, was ever used, and it continues to be used today, although the method has changed slightly.
In 1977, a German scientist shocked the world, claiming to have cloned three mice from embryos. Although embryos had been cloned before, no one had been able to do the experiment with mice because the cells were so small and the tools so large that the cells were traumatized and would eventually die after a few divisions. He instantly became famous, telling the world how he cloned his mice. However, he refused to actually demonstrate any of his techniques, and when other scientists couldn't replicate his work, he came under suspicion. He was challenged -- repeat his work or be discredited. He accepted.
He claimed to work nights and mornings when no one was around, but the equipment was never disturbed. He showed off his mouse embryos' growth daily, even though a malfunction in the water purification system left other scientists at his lab unable to grow other embryos. Later, in his cabinet, test tubes were found with mouse embryos in them, each at a different stage of development. Most scientists do not believe that this scientist was ever able to clone adult mice.
In 1978, a science fiction writer published a book claiming that a millionaire (known to the readers only as Max) had come to him because of his connections as a writer, and asked the him to arrange for Max to be cloned. The author eventually agreed, as the story goes, and Max was cloned. The book was ranked in the Top 10 list of popular books. Scientists who read his book, however, noticed discrepancies between the book and scientific data. One man who was quoted in the book was angry enough to sue. The publisher admitted that the book was a hoax, but the author maintains his claim to this day.
Within these two years, two front-page advances in cloning were discovered to be, most likely, frauds. As a direct result, many scientists began to claim that cloning of mammals was impossible. Funding and interest dropped, and cloning returned to the realm of science fiction for several years.
First Cloned Mammals
A breakthrough came in 1986. Two teams, working independently but using nearly the same method, each on opposites side of the Atlantic, announced that they had cloned a mammal. One team was led by Steen Willadsen in England, which cloned a sheep's embryo. The other team was led by Neal First in America, which cloned a cow's embryo. Many advances were made during the course of these experiments, including progress in keeping tissue alive in lab conditions. However, neither team believed that it was possible to clone from an adult's differentiated cells. With no progress in sight, the prospect of cloning fell by the wayside, and little research was done on the matter.
Ian Wilmut at the Roslin Institute in Scotland was assigned to a project in 1986. His goal was to create a sheep that produced a certain chemical in its milk. He chose to alter adult cells, which held up well in laboratory conditions, and then clone them, producing animals with the altered gene all throughout their bodies. He began the paperwork in 1987, and began research in 1990.
One of Wilmut's colleagues, who had experience with cloning from early embryo cells, suggested that the reason so many cloning attempts failed was that the cells were in incompatible stages of life. In one stage, the cells are adding to the DNA, in another, they are proofreading it, and in another, splitting it. The cells, he theorized, could not always start over. Wilmut's team learned that by starving the cells, they could be forced into what is called the G0 phase, similar to cellular hibernation. This advance increased the survival rate of the cloned cells; Megan and Morag, two lambs, were cloned from sheep embryos.
Wilmut's team now realized that differentiation did not matter in cloning. More work was done, and on July 5, 1996, a lamb was born, cloned from a frozen mammary cell from another adult sheep. Wilmut, who names his animals very creatively, named her Dolly after Dolly Parton.
Although Dolly was just a step in a long experiment, the press descended upon the first animal cloned from an adult. The Roslin Institute was overrun with journalists and reporters. However, other scientists were critical -- Dolly took 277 tries to create, and other labs were unable to reproduce the results. In addition, it took over a year for the institute to test Dolly's DNA to make sure that it was indeed the same as that of the frozen mammary cells. Science, although temporarily impressed, demanded a better way.
Herd of Mice
Oct 3, 1997, the Honolulu Technique created Cumulina the cloned mouse. She was cloned from cumulus cells (cells which surround developing egg cells) using traditional nuclear transfer. The nucleus was taken from the cumulus cell and implanted in an egg cell from another mouse. The new cell was then treated with a chemical to make it grow and divide. The scientists repeated the process for three generations, yielding over fifty mice that are virtually identical by the end of July, 1998. The Honolulu Technique's success rate of 50:1 is almost six times better than that of the Roslin Institute's success rate, 277:1. As cloning technology improves, more and more applications will be seen in everyday life.
How much do you love your dog? Is your dog so perfect that you would pay over $2.3 million dollars to have another just like it? One couple thinks their 11-year-old dog is just such an animal. Wishing to remain anonymous to avoid run-ins with the press, this couple has contracted Texas A&M University to clone their dog, Missy. Scientists are hailing this for its scientific achievement; no dogs have been cloned before because their reproductive system is rather complicated. If the cloning of dogs can be achieved, perhaps exceptional animals like rescue animals can be reproduced.
In addition to the pure scientific appeal of cloning a dog, the attempt to clone Missy has another interesting addition to make to the history of cloning. A private couple wants their dog cloned. They are, of course, spending millions to have her cloned, but consider the possibilities. Could cloning the family pet one day become a normal alternative to buying a new one?
Reliable cloning can be used to make farming more productive by replicating the best animals. It can make medical testing more accurate by providing test subjects that all react the same way to the same drug. It can allow mass production of genetically altered animals, plants, and bacteria. It may settle once and for all what part of personality is dependent on genetics and what part on environment. In short, it can be beneficial to almost every area of biological science.