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OU on the BBC: Background Brief - Cloning: The Story So Far

Updated Friday, 18th February 2000

First came Dolly... get the background on the issues surrounding cloning technology.

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Man taking photo of Dolly

If there’s a superstar of the animal world - it has to be Dolly the Sheep.
She absolutely loves the cameras and the human attention - and that’s just as well, because from the moment she was announced to the world by the Roslin Institute in Edinburgh, the media have been stampeding from all over the globe to get a look at her ...

A few years ago, most people would have associated the idea of ’cloning’ with those old sci-fi stories in which an evil genius manages to replicate an army of other identical evil geniuses... All total fantasy of course.

What Dolly proved, was that the cloning of mammals has become a technological reality. Which, amongst many other issues, throws up the emotive possibility that perhaps human clones could be the next logical step. But is that really the case? Janice Acquah set out to investigate...

First of she wanted to know: what exactly is a clone?

It boils down to one simple thing: if two organisms have identical DNA, then they’re clones.

So, for example, identical human twins are clones - even if you can tell them apart. And in other parts of the natural world, cloning is even more commonplace.

Bees Bees in a colony, for example, are clones of each other. And in the botanical world, plants like cactuses are clones of their parent plants, since reproduction simply happens when bits of the original plant drop off and take root. In other words, in any case where there is no fertilisation by another organism, the DNA remains the same = clones.

Deer We don’t know why clones are rare amongst animals but scientists believe that there is an advantage in maintaining substantial variability in a population. Evolution works by a process of natural selection from a variable population, and those characteristics that vary must be heritable. Clones don’t meet those requirements, and hence natural selection would act on all the individuals in the same way, instead of favouring ones most suited to the conditions present, as in a non-cloned population.

Janice and Dolly the sheep Critics sometimes talk about the cloning process as scientists "playing God". But agriculturalists have used cloning as a technique for developing and refining plant species for centuries, so in that sense, cloning is not new.
However, the process for cloning mammals is far, far more tricky than the agricultural process, and success in this field has been a revolutionary development.

The laboratory cloning process is extremely fiddly - involving minute manipulations which can only be observed through a microscope as they are carried out.

 

Cell 1

First of all an egg cell is taken from a mammal. These are about 0.1mm in diameter. The one shown here is next to a glass instrument that’s holding it in place using gentle suction.

The original DNA is removed from the cell. This DNA represents one copy of the mother’s genetic material - ie all the inheritance information relating to the egg cell’s donor.

Cell 2

This material sits as a discrete blob of matter on one side of the cell, so using a very fine pipette it’s possible to puncture the cell wall and extract it without destroying the rest of the cell.

Cell 3

Having removed the DNA, the nucleus of a cell from another adult is inserted into the egg cell. The animal this nucleus comes from is the animal which is to be "cloned". This nucleus has its own DNA, which will act as the blueprint for the characteristics of the resulting creature.

The amazing thing is that, although this egg cell has not been fertilised by sperm in the usual way, the cell will now begin to divide and become a growing embryo. This is then implanted back into the animal it came from - and if all goes according to plan, it should end up as a fully fledged animal...

Lambs They make it look easy. But it’s important to stress just how huge the failure rate is, at least at present. When Dolly was created, she was the one and only successful result out of 277 of these cell manipulation procedures. This is just one practical reason why many scientists say they would never try to create human clones - the emotional price alone would just be too high for the women involved, because of the high proportion of failures, and the fact that spontaneous abortions are commonplace in every phase of pregnancy, as are deaths in the early weeks after birth.

But getting back to Dolly. Her announcement didn’t just rock the world because she was a technological triumph. Her creation overturned one of the globally accepted "rules" of biology.

It had previously been believed that in the developmental process, once a cell takes on a specific function, there’s no going back. For example, once a cell becomes a kidney cell, heart cell or nerve cell, it can’t then turn into any other kind of cell. But what the researchers at the Roslin Institute had demonstrated with Dolly was that an adult cell - in this case a mammary cell - could be made to act like an embryo cell, which could go on to form a whole animal.

Since the famous sheep was created, scientists have produced clones from adult cows, goats, mice and pigs. Although sheep clones, notably Dolly, have already had offspring, it’s only very recently that another type of clone could be added to the breeding list. A cloned cow has given birth naturally to a calf in Japan.

So she’s certainly revolutionary in terms of her impact on science. But in other respects, is Dolly ’normal’?!

Stories on the Internet have claimed that she is "evil", and "a creation of Satan" ... but then that’s the Internet for you. She certainly appears to be a very healthy, and highly socialised animal. The staff at the Institute say she behaves like a family dog more than the timid sheep you might imagine.

And physically? She’s certainly fertile - she’s had several lambs.

But there is one hovering question mark so far, which relates to the possibility that she may be ageing faster than a normally-conceived sheep.

We all accumulate mistakes in our DNA as we get older - and this is true of animals such as sheep just as much as humans. Under the microscope, you can see that the ends of the chromosomes begin to get shorter over time as the animal/person ages. Dolly’s chromosomes show that effect more than would another sheep of her age - so she may have inherited the ageing effects which her mother’s DNA already had accumulated when the cloning was done. It will take a few years to ascertain this, but if it’s true then it’s obviously a serious side-effect of the process, and would represent another serious argument against human cloning being carried out in the future.

Update: Since this page was first published, Dolly has been put down. She developed arthritis at the age of five; at six, she was found to have a progressive lung disease usually found in much older sheep and it was decided to bring her famous life to a peaceful close.

First broadcast: Friday 15 Oct 1999 on BBC Two

Explore cloning further

Dolly the sheep Copyrighted  image Icon Copyright: BBC

Due to the huge public and professional interest in the latest developments in cloning there are many websites and many books available on the subject. A large proportion of these are concerned with human cloning and in particular, the ethics of human cloning, should it ever happen. You won’t have to look far for these - so what’s listed below are resources which primarily focus on the practical and scientific aspects of the technology.

Websites

... for a comprehensive introduction - and some great FAQs:
New Scientist - Cloning Report: Everything you always wanted to know...

The Australian Academy of Science: The Mammal Copiers - Advances in Cloning

... and to keep tabs on the Roslin Institute, where Dolly and other mammalian clones have been created, this site includes an archive of their press releases and explanation of the technology involved:
The Roslin Institute Online

... and if you want to know more about xenotransplantation - the use of animal organs for transplants:
The United Kingdom Xenotransplantation Interim Regulatory Authority

... and finally, if you’re interested in genetics generally, here’s a site which hosts links to just about every genetic subject going:
Genetics: Virtual Library

Books

... for the inside story on the cloning of Dolly:
The Second Creation
-  Ian Wilmut, Keith Campbell, Colin Tudge.
Published by Headline Books

... for a general introduction to the science of cloning:
The ABCs of Gene Cloning
-  D.W.S. Wong
Published by Kluwer Academic Publishers

 

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