Cloning and genetic engineering

What is genetic engineering?

Genetic engineering (GE) is the manipulation of genetic material (ie, DNA or genes) in a cell or an organism in order to produce desired characteristics and to eliminate unwanted ones. GE includes a range of different techniques with many different uses, and can be applied to plants, animals and humans.

For example, the genetic modification of food is a form of GE that involves manipulating the cells of plants such as maize, to increase the yields, make it more nutritious and to make it drought- and disease-resistant.

However, the most contentious type of GE is definitely related to its applications in humans. GE in humans has opened up a Pandora’s box of possibilities as it can be used for both the miraculous and the sinister.

The cloning of Dolly the sheep in 1996 was a very important event. Until then, the cloning of a human was only possible in theory. Recent films and TV programmes such as Gattaca, Mutant X, Dark Angel and books such as Brave New World all focus on possible consequences of this technology – but what is the real deal?

What is cloning?

If you were told that there was a clone of you sitting in the next room, what would you expect the clone to look and act like?

Probably, exactly the same as you. But, despite all the movies and TV programmes that have explored the possibility of exact clones, it is highly unlikely that a clone of you would look exactly the same and would certainly not act exactly the same.

A clone is not completely genetically identical, as there are small differences in the genetic make-up just as there are with identical twins. Despite the fact that identical twins come from the same egg, after a while one begins to notice the differences between them in order to tell them apart. It has been discovered – by doing a number of studies on identical twins brought up in the same environment – that genes mysteriously react differently to the same environment.

While cloning a whole human is certainly the ultimate challenge for genetic engineers, cloning is not limited to this goal. Cloning can be, and is, done on a much smaller scale and could involve no more than just the cloning of a single cell. Therefore, cloning can be divided into two types:

  • reproductive cloning (which is the cloning of a whole organism); and
  • therapeutic cloning (which is the cloning of cells or even organs or other tissue for transplant purposes).

Due to the fact that genetic differences are likely to exist between a clone and its donor, this uncertainty has led to many countries banning the reproductive cloning of humans.

How are clones made?

Reproductive cloning:
In order to make a clone of someone, one needs a living cell and a human egg (ovum). The nucleus of the egg, which contains the DNA, is removed and replaced with the nucleus from the cell of the person/animal to be cloned.

A short electrical pulse then stimulates the egg to start dividing and the embryo is then implanted into the womb where it develops into a duplicate of the person that donated the cell nucleus. Clones created in this way are not 100% genetically identical, as there is some DNA from the original egg cell that is found outside the nucleus (mitochondrial DNA).

Therapeutic cloning and stem cells:
In therapeutic cloning an embryo is created in the same way as reproductive cloning, but it is not implanted into the womb of a woman. Instead, stem cells are extracted after the embryo starts dividing in the first 14 days after fertilisation, which kills the embryo. Stem cells are special cells with the ability to reproduce and become one of 300 types of cells, eg, skin, liver cell, hair or blood cells. These cells are then used to grow the specific type of tissue or organ that is needed and has the advantage of being genetically identical to the patient who donated it, eliminating the problem of organ or tissue rejection. Currently, if someone has an organ transplant, there is quite a high possibility that their body will reject the foreign organ and so they not necessary have to suppress the immune system to lessen the chances of this happening. Stem cells could potentially be used to repair damaged or defective tissues around the body, such as the cells in the pancreas that stop producing insulin in diabetics.

Adult stem cells versus embryonic stem cells

The problem with embryonic stem cells is that many people feel that by using a human embryo and then killing it, you are actually killing a potential person. It is for this reason that the United States and other countries are calling for a global ban on all human cloning, including the use of embryonic stem cells. As a result, there has been new research into the potential of what is known as "adult stem cells".

More than 30 years ago it was discovered that, in addition to being found in embryos, stem cells are also found in adults. Adult stem cells can be removed from a person without causing any harm. Until very recently, it was thought that adult stem cells were only suitable for cloning a few types of cells and tissues. However, new studies have found adult stem cells with almost the same abilities as embryonic stem cells in various human tissues, including: the spinal cord, the brain, connective tissue and in the blood of the umbilical cord.

These studies have shown that it is possible for us to manipulate cells to take on new functions/start doing different jobs simply by placing them in different environments and "reprogramming" them. For example, neural (brain) stem cells in mice have been transformed into the blood stem cells that produce the different types of blood cells. In other animals, bone marrow stem cells have become brain cells and liver cells. In humans, bone marrow stems cells of a patient have been transplanted into the areas of the heart damaged by a heart attack, triggering new growth of heart tissue.

Although adult stem cells are already being used successfully to treat a number of diseases, there are a number of problems to be overcome, such as finding and extracting the adult stem cells. Embryonic stem cells have not yet been used for therapy and research is still in the initial stages. Eventually, it may be that, rather than just one type, both types of stem cells will be used for different purposes – whichever proves to be the best for the situation. In the meantime, parallel research continues on both cell types. See www.stemcellresearch.org for more information.

Potential uses of cloning

Although currently the risks of cloning outweigh the possible benefits, there are many different potential uses of human cloning technology:

  • Replacing organs and other tissues – such as new skin for burn victims, brains cells for those with brain damage, spinal rod cells for the paralysed and complete new organs (hearts, liver, kidney and lungs). Pigs are also being genetically modified to make their organs more compatible with humans by removing the gene that causes rejection. People could have their appearance changed (cosmetic surgery) using their own cloned tissue and accident victims and amputees could also benefit from this tissue regeneration.

  • Infertility – human cloning provides couples and individuals who are unable to have children with another potential option.

  • Replacement of a lost child – parents who have lost a child through an accident or an illness could clone an identical "replacement" child.

  • Creating "donor" people – cloned people could be created to provide a source of transplant material.

  • Gene therapy – cloning technology could be used to prevent, treat and cure genetic disorders by changing the expression of a person’s genes. This technology may also provide the cure for cancer by revealing how cells are switched on and off. Gene therapy could be used to treat somatic (body) cells where the change is not passed on to children, or germ (egg and sperm) cells where the changes are passed on.

  • Saving endangered species – by boosting their numbers through creating clones. However, since clones are almost genetically identical, the genetic diversity of the species would not be increased.

  • Reversal of the ageing process – once more is understood about the role that our genes play in the ageing process. However, some of the above uses carry with them some serious ethical implications.

Problems with cloning techniques

Dolly the sheep was created in 1996 using the cloning methods outlined above. Although Dolly was born looking normal, she has suffered from several problems associated with the cloning technique, including premature arthritis, which is thought to be a side-effect of the cloning. Other problems with the current cloning techniques, include:

  • Low success rate: Dolly the sheep was successfully cloned, It took 276 unsuccessful attempts before it worked. Similar work on mice and other mammals has also produced the same statistics. To date, the success rate (on animals) is 3-4%.

  • Tumours: Embryonic stem cells are unstable and difficult to control. They have a tendency to uncontrollably divide leading to tumours/cancer.

  • Genetic defects: Although the original DNA from an embryo is removed and replaced with the nucleus from the person to be cloned, some DNA from the original embryo remains in the form of mitochondrial DNA. This can lead to genetic defects that are not fully understood and which are only seen in later life.

  • Over-growth syndrome: Clones of animals are larger than average at birth, which can be risky for the mother.

  • Premature ageing: The age of a clone is calculated by taking its birth age and then adding the age of the original from which it was cloned. Although Dolly was born in 1996, she originates from the udder of a sixyear- old ewe and so her total genetic age is almost 13.

  • Massive quantities of human eggs required: If applied to humans, the current method of cloning would use a vast number of human eggs. To provide these eggs, women would have to become "egg factories", and harvesting them is both painful and dangerous. If adult stem cells were used, then human eggs would not be required as cells could be obtained from the patient without harming them.

  • Reduction in adaptability: Since, by nature, a clone is a copy of another person, there would be no unique genetic combinations introduced into the human gene pool if human cloning was undertaken on a large scale. Therefore, if a contagious disease struck for which there was no cure, all the clones would be wiped out.

  • Insertion of the gene: In gene therapy where a healthy gene can be used to replace a defective gene, viruses are usually used to insert the gene into the person’s cells. The virus injects the healthy DNA into the cells and the genetic defect is corrected. However, this is not always successful as the virus cannot always be controlled and has triggered leukaemia in a recent clinical trial in France.

  • Lack of knowledge: Although the Human Genome Project has mapped out where the different genes are, a lot more information is needed on their functions. In some cases, a single gene may have more than one function, and in others several genes can cause a genetic disease.

Where is cloning allowed?

Around the world, different countries have different rules relating to cloning – some don’t allow reproductive cloning, but do allow therapeutic cloning, while other countries allow both types.

In South Africa currently, the Human Tissue Act prohibits both therapeutic and reproductive cloning of humans. This situation will change when chapters 6 and 8 of the National Health Act are promulgated - and therapeutic cloning will then be allowed under strict conditions, requiring Ministerial permission, but reproductive cloning on humans will remain strictly prohibited.

In China, there are no laws against cloning either. However, with the huge population problem and the policy of only one child per family, there is no interest in reproductive cloning. On the other hand, there is huge interest in therapeutic cloning and, as a result, there is a lot of it on the go in China. Some Chinese cultures believe that humans only become people when they participate in society – so, according to these cultures, embryos and foetuses are not considered to be human beings, thereby eliminating any ethical problems surrounding the creation and destruction of embryos to get the required stem cells.

The Chinese government is funding extensive research and drawing back many Chinese scientists from overseas, to undertake work they would not be allowed to do elsewhere. With easy access and no limits on obtaining the embryonic material they require, it is expected that Chinese scientists will race ahead of the rest of the world in therapeutic cloning technologies.

In the UK there are clear rules banning reproductive cloning, but scientists in both the UK and Israel are allowed to generate new embryonic cell lines for therapeutic research. The law in Germany bans the extraction of stem cells from human embryos for research within the country, but in 2002 a new law was passed allowing some human embryonic stem cells to be imported. This means that German scientists are allowed to undertake work on embryonic stem cells if they originate from outside Germany.

In the United States there is no public funding for research on embryonic stem cells. Therefore, although there is no law against therapeutic cloning in the US, there is almost no public research happening due to the lack of money and access to the embryonic material. Simultaneously, an announcement was recently made stating that US public funds (about US$1,4 million, about R11,2 million) will be provided for studies using adult stem cells instead of embryonic stem cells.

These different rules for different countries mean that if a scientist is banned from undertaking cloning in his/her home country, he/she can simply move to a country where it is allowed. To prevent this from happening, the US and about 30 other countries want a global ban on all forms of cloning. However, many countries don’t agree and thus no progress is being made on implementing this ban.