National Anti-vivisection Society

 

National Antivisection Society

Welcome to the Freak Show

(NAVS Campaigner January - April 2002)

There is a worldwide explosion in new technologies relating to the manipulation of genes. Huge media interest is being generated in any bizarre development, regardless of how vague or remote, the potential human application. However, share prices of genetic modification companies can soar on the back of extravagant claims.

These biotechnologies are incredibly hit and miss, cause extreme suffering and downgrading of animal life, and the long-term complications are unknown.

What the vivisectors are attempting

Cloning: Our genetic material (DNA) resides in each of our cells (mostly in the nucleus, at the centre), where the genes are arranged along a pair of chromosomes. In theory, we can be completely replicated from one of our cells - a clone is an identical copy of a living organism. The main method is by taking a cell from an animal (usually an embryo), taking out the nucleus, and inserting the nucleus into an egg from another animal, from which the nucleus has been removed. The egg is implanted into the womb of a surrogate mother, and if the infant is born, it is an identical copy of the animal from which the cell was derived. By taking more than one cell from an animal, multiple clones can be created, identical to each other and to the original animal.

Genetic Modification is when the genes of one animal are inserted into the egg of another animal to either add a foreign gene (transgenesis), or when specific genes are targeted to remove them (knock out). If successful, when the animal is born it will have the desired genetic trait. Animals are being created with, for example a human gene believed to make people susceptible to a certain cancer, or with a human gene in the hope that one day they might supply spare organs for transplant into humans. Others have been modified for producing drugs in their milk, and a host of other purposes.

Linking the technologies: If the two technologies were to be brought together, i.e. create a genetically modified animal that, say, produces a product in its milk that can be used for a new drug, and then clone that animal, the result would be a group of identical animals producing products on a factory production-line scale.

GM organs

There is a shortage of human donor organs. Some animal experimenters believe the answer is to create genetically modified (GM) pigs as a potential source of organs for humans (xenotransplants). GM pigs have been created with a human gene, for example, in the hope that the human body will not recognise the transplanted organ as ‘foreign’ and reject it (1).

The whole process of genetic manipulation causes prolonged distress and suffering to the animals, including surgery, egg collection, egg implantation, and repeated blood and tissue sampling for the offspring, to check whether they have taken up the desired gene. Another problem is the high failure rate, only about 10% of the offspring carry the new gene, the others are discarded.

Now, researchers hope to modify pig clones to express traits desirable for xenotransplantation. In a preliminary experiment, US researchers produced cloned pigs with yellow snouts and hooves that glow under ultraviolet light. The University of Missouri team inserted jellyfish genes into foetal pig cells grown in the laboratory. The central part of the cells, the nucleus containing the DNA, was removed and placed inside pig eggs from which the DNA had been removed. Finally, these ‘reconstructed’ eggs were implanted into a surrogate mother resulting in the birth of five piglets in March 2001, four of which displayed the yellow colouring. The jellyfish colour indicated that the cells had taken up the gene. The researchers claimed that the experiment is a step towards developing pig organs that will not be rejected by the human body, because the experiments showed that it would be possible to use the same technique to add human genes to cloned foetal pig cells, grown in the laboratory (2,3). These experiments utilise two established techniques: The cloning of animals with a human gene, and insertion of jellyfish genes into animals (4,5).

Cloning

The cloning of animals is a seriously flawed technique; the majority of animal cloning experiments result in deformities, miscarriage and stillbirth (6). Furthermore, news broke early this year that Dolly, the first sheep to be cloned from an adult cell, has developed arthritis, prompting concerns about the future of cloning (7). Dolly is now five years old but the udder cell from which she was cloned was from a sheep aged six years (8). Sheep usually live until around 13 years (9), so if Dolly is really an eleven year old, she’s no youngster. (The makers of Dolly had hoped to produce clones which had been genetically modified to produce a human protein in their milk, thus forming a production line).

In May 1999 researchers of PPL Therapeutics at Roslin in Scotland, where Dolly was cloned, discovered that Dolly had shorter telomeres than other sheep her age, arousing suspicions at the time that she may be prone to premature ageing. Telomeres are pieces of DNA at the end of the chromosomes and are linked to the ageing process. Chromosomes contain the genetic material and divide when the cell divides. Telomeres eventually erode after a number of cell divisions, and when they are gone the cell dies. The six year old cell from which Dolly was cloned already contained shortened telomeres (10).

Arthritis is not commonly found in a sheep Dolly’s age. “We will never know in the case of Dolly whether this condition is because she is cloned or whether it is an unfortunate accident that she developed this condition” said Professor Ian Wilmut of Roslin who led the team that cloned Dolly (7). The cloning of Dolly raised the hopes of companies who wanted an endless supply of identical animals with organs genetically modified for use in people (11), yet there is a chance that shortened telomeres could be passed to offspring (10).

Combining Biotechnology

A few days prior to the disclosure that Dolly has arthritis, PPL Therapeutics announced that they have produced a litter of five cloned female piglets, Noel, Angel, Star, Joy and Mary, born on Christmas Day 2001 at their US subsidiary in Virginia. PPL says this is a step further towards xenotransplantation as one of a pair of genes responsible for making a chemical that causes a transplanted pig organ to be rejected by the human body, has been knocked out (12). This is considered to be a step forward because one of the problems of transplanting animal organs into humans is that the human immune system mounts a severe and immediate attack on the invader, termed ‘hyperacute rejection’. The researchers cloned foetal pig cells from which only one copy of the gene had been removed. For any chance of success in using the pigs’ organs for transplants, they would need to be lacking both copies of the gene but Jeffrey Platt, director of transplantation biology at the Mayo Clinic in Minnesota pointed out that this could be lethal to the pigs. Furthermore, according to virologist Robin Weiss at University College, London, other similar substances remaining in the animal organ may cause hyperacute rejection (13).

Hyperacute rejection is not the only way in which xenotransplants can be destroyed, however. There are natural killer cells in the human immune system that will attack the tissue. Also, incompatibility between the pig and human blood clotting system could cause the formation of massive blood clots in the transplanted pig organ and other parts of the patient’s body. Also, T cells which cause a slower, but more severe, form of rejection are hard to control by conventional drugs designed to suppress the immune system (14). Many monkeys and baboons in transplant experiments have suffered in experiments where, despite being pumped full of immunosuppressive drugs, none have survived more than a few months (15).

Immerge Biotherapeutics, a rival US company backed by Novartis, said it has produced similar ‘knocked out’ pigs (16). The team had to implant over 3000 embryos, produced from cloned foetal cells (from which the unwanted gene had been knocked out) into 28 surrogate sows to get 7 live piglets, 3 of which died (11). Hugh Auchincloss, a researcher at Massachusetts General Hospital in Boston and an adviser to Immerge Biotherapeutics said the purported breakthrough may be “just another layer on a dense onion of xenotransplants issues” (14). Furthermore, the large quantities of immunosuppressive drugs a recipient will need to take during their lifetime to prevent organ rejection in the long-term, renders the patient vulnerable to cancer or life-threatening infections (17). Despite the obstacles, Immerge say they hope to be ready for human clinical trials in three years, after non-human primate clinical trials are completed (13).

Epidemic Risk

PPL plans to make further genetic changes to the knockout pigs to try to prevent other forms of rejection (14), but the research does not address a different threat to the human population. There may be unknown viruses (porcine endogenous retroviruses or PERVs) in the animal tissues that could pass to humans and cause serious outbreaks of disease in the future. The likelihood of this happening is exacerbated by the fact that transplant patients need to take drugs to suppress their immune system (18).

With the obvious ethical and safety concerns regarding cloning perhaps animal researchers will not be so quick of the mark to announce another cloning “success” (7). Dolly’s affliction has already had a negative financial impact on PPL Therapeutics plc. The company’s announcement that it had produced cloned piglets as a step towards organ transplants saw a surge in its shares, by 44%. However, the disclosure of Dolly’s arthritis on 4th January caused them to plummet by 16%(7). PPL now wants to raise 20 million, possibly by the involvement of a large drug company, to further develop the so-called treatment for people (16).

But, as New Scientist pointed out: “The commercial hype surrounding xenotransplantation often obscures the fact that the obstacles to success are still colossal” (15).

This is yet another development in the area of animal research that gives seriously ill people false hope, and diverts resources and attention from alleviating the shortage of human organs.

References

1. Mepham TB et al. The use of transgenic animals in the European Union. The Report and Recommendations of ECVAM Workshop 28. ATLA, 26, 1998: 21-43. In ATLA Supp.1, vol. 27, Nov/Dec 1999.
2. The Guardian, 13 October 2001: 15.
3. Daily Mail, 12 October 2001: 3.
4. Schnieke et al. (1997) Human Factor IX transgenic sheep produced by transfer of nuclei from transfected fetal fibroblasts. Science 278: 2130-3.
5. Science (5 January 2001) 291: 226.
6. The Guardian, 8 August 2001.
7. Wall Street Journal 7 January 2002: 9.
8. Wilmut, I; Campbell K; Tudge, C. The Second Creation. The age of biological control by the scientists who cloned Dolly. Headline Book Publishing (2000).
9. New Scientist, 12 January 2002: 11.
10. Cloning and the clock. Science and Genetics; Financial Times 27 May 1999.
11. Science, 4 January 2002; 295: 25-6.
12. Guardian 3 January 2002: 1.
13. Nature, 10 January 2002; 415: 103-.
14. New Scientist, 12 January 2002: 7.
15. New Scientist, 12 January 2002: 3.
16. Independent on Sunday, 6 January 2002: 3.
17. Xeno. The promise of transplanting animal organs into humans. Cooper, KC & Lanza, RP. Oxford University Press (2000): 85.
18. Stoye, JP et al. (1999). Endogenous retroviruses: a potential problem for xenotransplantation? Ann. NY Acad. Sci.; 30 (4): 390-6

(NAVS Campaigner January - April 2002)

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