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Author: Mark Hirst

The biology of cloning

Updated Thursday, 3rd August 2006

What happens during cloning? Mark Hirst explains.

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What science is involved in cloning?

"There are several issues to do with stem cells and cloning and how people fail to delineate between the different types. Stem cells are cells that are capable of generating all the tissues in the body and classically they've been looked at mostly in the mouse. These are cells which can be grown indefinitely in a laboratory situation which when you take them out of those conditions you can turn them into insulin-making cells or dopamine-making cells. Then, when they're put back into the body, in this case the mouse, they colonise and reform.

So stem cells have now been derived from humans and there are about twenty or thirty stem cell lines around in the scientific community that people are experimenting with. So you can use stem cells and turn them into therapeutic agents for curing patients. There's been a lot of debate, particularly in the U.S., about funding work for these, because these lines are derived from embryos. In the states now George Bush has just announced that people will be able to work on the lines but they will not be allowed to generate any more lines. This is to solve the moral problems of destroying an embryo to create the lines.

So stem cells are already being studied and in some cases developing into therapies. Cloning is a rather separate issue because cloning involves taking a somatic cell - that is a cell that's not in your germ line, for example, a skin cell, a liver cell, a kidney cell, a muscle cell - and turning that back into an embryo cell. The process created Dolly the sheep.

Compassion In World Farming protest against cloning
Making a stand: Compassion in World Farming protest in Trafalgar Square against cloning

What happens during the process of cloning?

The process of cloning effectively involves taking a cell from your body and turning it back into an embryo. The embryo would then either develop into a human being as has been proposed by various scientists around the world and which is currently banned, or it would be turned into a stem cell. In terms of cloning, what you produce is an identikit cell - a cell which was personalised for you or personalised for me. This means that it can get round some of the issues, for example, of having an immune reaction.

If you take a cell line from somebody else, there's always a possibility that your body would react to it. Whereas if it comes from you, it's your own - it's personalised. That is really where the issue of cloning comes in with regards stem cells.

What is actually done in the laboratory?

Cloning effectively involves turning a normal cell from your body back into an embryo. The reason Dolly was such an amazement was because scientists didn’t believe this could happen.

What you do, in order to turn a cell back into an embryo, is you take an egg. An egg contains all the right environment from which an embryo will develop. However, the egg has also got a nucleus in it, it's got DNA in it, and you want to get rid of that.

The first thing they'd do is they'd take out the DNA from the egg, so you have an empty egg, rather like an empty tennis ball. Then you take the cell from your skin and you take the DNA from the nucleus and you pop it into the embryo. This is why it gets its other name which is, ‘nuclear transfer’ or ‘genetic transfer’.

You’re taking the genetic information from you, from your skin cells, and you’re popping it into an embryo. Then you let that egg, or a newly formed embryo, develop and it goes through the normal stages of development: it divides into two cells, into four cells, into eight cells, into sixteen cells, and then forms into an embryo.

So effectively all you're doing is taking the genetic material from your skin cells and popping them into an egg to make an embryo. It's a simple transfer process which is very inefficient.

How is the DNA removed?

You have a very small little sucker and you punch a hole into the egg and suck out the existing DNA. Then you do the opposite: you suck out the DNA from the skin cell and pop it in. It's rather like a miniature vacuum cleaner that sucks and it can also squirt. This is done under a microscope in a laboratory, under what's called sterile conditions because you don’t want to get fungus and bacteria growing.

When was this science first put into practice?

For cloning, the original experiments were all done in the mid-1990s that resulted in the creation of Dolly the sheep. Since then, cloning has been used on cows, pigs, some primates, some monkeys and extensively with mice. Because mice are used a lot in laboratory experiments, we know a lot about how processes work in mice.

Some of the reasons why this science has been done is for commercial reasons. For example, if you have a prize bull that's worth several million dollars and is about to keel over, if you can make copies of him. You can see the obvious commercial applications.

But there's been a lot of interest in working out whether or not the process of cloning is actually viable. Because Dolly the sheep was the only one of 250 experiments that worked - the rest all failed. The question is: if this is ever going to be used therapeutically for humans is it ethical to think about doing a process on humans which is so inefficient and possibly damaging.

How is stem cell cloning different from human cloning?

The use of stem cells for therapy is very well established in the mouse field. Scientists have been working on embryonic stem cells in the mouse for almost twenty years. It's important to remember that whilst a stem cell in the mouse will turn into a fully blown mouse, it does this in a very developmentally programmed way.

We don't understand how it does it but it turns into a mouse. That's a property of two things. First of all the cell itself knows what it has the potential to become but it also has to react to other things around it. So a liver, for example, doesn't develop as a liver separately, it develops as a liver in the context of all the other organs and all the other body tissues. So in a culture of these cells, what scientists have had to work out is how you reproduce those signals.

How would you take cells and push them into becoming a liver cell, or push them into becoming an insulin-secreting cell?

People have worked out ways of doing this in the mouse. So, for example, there are ways of making cells which produce dopamine which might be therapeutic for Parkinson's disease. There's no reason to believe that human stem cells, which [are relatively new discoveries] (they were first isolated in 1998), would be different in any way. What it means is that we can apply twenty years of knowledge from the mouse probably directly to the human lines and hopefully be able to produce therapeutic lines within the next ten years.

Is the public's perception about cloning wrong?

Public misconception often happens around cloning. They tie in what they've heard about developments in genetics and embryology and assume that they're one and the same thing. For example, that the human genome project has something to do with cloning - well it doesn't. Cloning is an embryological technique that has really very little to do with genetics. Its applications are in curing disease.

One of the big problems is that on virtually every television programme about cloning, there will be somebody standing there presenting and saying, "what happens if I clone myself?" and an immediate copy will appear next to them. Well, if we ever were to allow cloning to happen for humans we would generate a baby. So, a clone of myself as a forty year old male, would generate a bouncing baby boy. It would be genetically the same as me but would not be what we think of as a clone - it would not be an identikit copy. It would grow up in a new environment and its personality or lots of its genes would be influenced heavily by that environment. So the idea that cloning will produce identical copies of Tony Blair or Margaret Thatcher or Adolph Hitler, is just hopelessly misconceived. So that's the first major misconception.

The second misconception is that people are going to do it. There is only one person in the world, who realistically has said they're going to do it, which is an Italian scientist who's been ostracised effectively from the world community of both scientists and biologists and clinicians. There is a great feeling amongst the mainstream scientists that this process shouldn't be done: it's inefficient and has very major moral and ethical problems. There will always be somebody who will try it and I don't suppose you can control things like that.

What future application is possible?

Over the last five years or so, people have done extensive analysis, particularly in mice, and asked whether or not the mice you generate are healthy mice or whether they have problems. It’s become apparent that a lot of DNA damage, a lot of genetic problems, are arising in the mice that had been generated and this is one of a lot of evidence which suggests that the use of cloning to create a human individual, a live born baby, would be unethical.

Not only is it very inefficient, but you're probably standing a very high chance of creating people with risks of cancer, with genetic abnormalities and all sorts of other problems. So cloning has moved on a lot. But in terms of its application to humans, there have only been a few experiments, and most of them are involving very early embryo genesis, so the first sort of four or five days

What could cloning’s impact be for humans?

In terms of its influence on medical care, the major impact will be in the production of personalised stem cells. The most immediate effect may actually come from the commercial side of its use with animals. One of the reasons why cloning was developed at the Roslin Institute was as a way of making large numbers of copies of very valuable breeding stock. And one of the projects that they're working on at the Institute is to produce sheep that secrete valuable human hormones in their milk. If you can create sheep that are producing, for example, Factor Nine, a clotting agent that's used to control haemophilia in humans, it may be more bioactive. I can see things coming from that line far more quickly than I can ever see them becoming used in the human line.."

This article was first published in 2001


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