SCOTTISH scientists are creating pigs that are genetically modified to suffer from incurable human diseases – so they can be used by drug companies to test new therapies.
• Genetic modification has produced pigs that glow in blue light – now the Roslin scientists hope to use the technique to produce animals suffering from human diseases to aid research into cures. Picture: Complimentary/The Roslin Institute
The team of researchers is trying to produce pigs which are diseased with the lethal lung condition cystic fibrosis and an eye disease that leads to blindness in humans, The Scotsman has learned.
The highly controversial research is being carried out at the Roslin Institute in Edinburgh, famous for creating Dolly the cloned sheep. If the team is successful, the diseased animals would be used by drug companies to test potential new gene therapies for the conditions.
The cutting-edge research raises major ethical issues about harming animals intentionally for the benefit of humans. It has led to outrage from animal rights organisations.
In a frank interview with The Scotsman, Dr Bruce Whitelaw, head of developmental biology at the Roslin Institute, admitted he had struggled with the idea of creating diseased animals purely to try to benefit humans.
"We are saying we will make these animals sick purely for our benefit," he admitted. However, he believes his team has a "moral right" to give the technique a try.
His work will be the subject of a debate tonight at Edinburgh Zoo on the ethics of genetically modifying animals.
Cystic fibrosis is an incurable hereditary condition that often leads to death in the early twenties. It is one of the most common life-threatening inherited diseases, affecting more than 8,500 people in the UK, including the son of the former prime minister, Gordon Brown.
Retinitis pigmentosa is the name given to a group of hereditary diseases of the eye, which affects about 25,000 people in the UK. It is a progressive genetic disease that eventually leads to blindness.
Dr Whitelaw said the pigs would be used as "models of the human diseases" to provide a better way to test potential treatments.
Existing options involve using mice, which he said were "inadequate".
Dr Whitelaw believes there are theoretical reasons why pigs should be good models for human disease – because of many physical similarities, such as similar eye size.
However, he acknowledged that creating the diseased animals would "not necessarily" allow treatments to be developed.
But he said that, since the Roslin had managed to develop the techniques to modify the animals in this way, they should find out if it could help to find cures.
"We have this technology. It's really important to try to see if it can help. It may not, in which case we should stop.
"I don't think we should use this technology for something we can currently treat just so we can make the treatment slightly better, but we should use it for diseases that we don't have treatments for," he said.
He emphasised that, if the technique turned out not to be useful for finding treatments, he would be arguing "as strongly as anyone else" that it should no longer be used.
"But we should find out," he added. "I believe we've got a moral right to find out."
Dr Whitelaw believes it will take at least two years to produce the genetically modified pigs, and another two years to find out whether they could be treated.
He continued to justify the work by adding: "If we believe we need to have therapies for these diseases – and currently society en masse believes that – then we surely have to have that tested in the best way we can before it goes into that patient.
"Then the better the animal model – the more likely it's going to tell you something about going into a human patient – the better.
"And basically mice are mediocre at best and the majority of studies are done on mice."
The work at the Roslin Institute, which began last year, is unique in the UK.
So far, the scientists have not successfully created animals with the diseases.
The technique involves the use of viruses to carry chosen genes into fertilised eggs.
Once altered, the eggs are then implanted in surrogate females, so that theoretically animals are born with the genetic conditions.
The resulting pigs are a type of what is known as a transgenic animal – creatures that have inserted DNA that originated in a different species.
Already, to prove genes could be successfully inserted into animals using the technique, pigs have been produced at Roslin that carry a green fluorescent protein gene found naturally in jellyfish.
The animals have a greenish tinge in normal light and when viewed in blue light they glow. This was done to provide the scientists with a genetic marker – a physical manifestation of how the pigs had been modified.
The work at the Roslin Institute will be the subject of a debate called "After Dolly… where do you draw the line?" at Edinburgh Zoo tonight, when Dr Whitelaw will be joined by Peter Sande, professor of bioethics at the University of Copenhagen, Denmark.
Animal rights groups reacted with horror at the news.
Andrew Tyler, the director of Animal Aid, said the techniques involved the "intrusive, harmful, painful experiments on animals" and should be banned.
He also believes the science behind the research is flawed.
"This type of work leads to an enormous attrition rate of animals being born malformed or dying in the womb," he said.
"The gene that is being added is being put in a different species and it interacts with all sorts of other genes so you cannot extrapolate from these altered animals to people.
"This should stop. It's cruel and it's scientifically fraudulent. It's also fraudulent to the people who will think a cure is imminent, and it's an intolerable imposition on the animals concerned."
Dr Jarrod Bailey, scientific adviser for the British Union for the Abolition of Vivisection, argued that animals could not be used to predict whether a new treatment would be safe in people.
"Animal research is a failure. Around 100 Aids vaccines, over two dozen diabetes treatments and hundreds of treatments for stroke, Alzheimer's, Parkinson's, cancer and many more diseases – worked in mice, monkeys and even chimpanzees, yet failed in humans.
"Genetic modification has failed to overcome species differences at the root of these failures."
And he added that it was cruel.
"Pigs have cognitive abilities more advanced than three-year-old children, ranking behind only dolphins and non-human primates," he said.
Libby Anderson, political director at Advocates for Animals, said it made her "despair".
"It's depressing to hear this repeated focus on modified and mutated animals, when there is so much potential for non-animal research," she said.
"It sounds like they are going down a blind alley, and even in the scientists' mind it is clearly raising huge ethical issues."
The Scottish SPCA was also opposed to the work, but chief superintendent Mike Flynn added that he acknowledged that "for the time being" animal testing was "required before essential medicines can be made available to relieve suffering in humans and animals".
He added: "Thankfully, there have been improvements in this area in recent years and animals can only be used to help develop cures for life-threatening or debilitating disease."
Experiments such as those taking place at the Roslin Institute are scrutinised by the Home Office Inspectorate and are licensed following consideration of the expected benefit and the welfare cost to the animals.
Dr Whitelaw told The Scotsman he was looking forward to hearing the views of the public at today's debate.
"I think anyone is entitled to any opinion they have got," he said. "I think the strength of a society is that we have grown-up debates and come to a conclusion. If society came to the conclusion that we shouldn't do this, then I would accept that. I would think it was a wasted opportunity, but I would accept it."
At the cutting edge of research
THE Roslin Institute was established in 1993 as a wholly-owned but independent institute of the Biotechnology and Biological Research Council (BBRC). Its antecedents, however, go back to 1919 and are closely linked to animal genetics research at the University of Edinburgh.
Its mission is to gain fundamental understanding of genetic, cellular, organ and systems bioscience underpinning common mechanisms of animal development and pathology, and to drive this into prevention and treatment of important veterinary diseases and develop sustainable farm animal production systems.
Based in the Midlothian village from where it takes its name, the institute is due to move next year to a 60.6 million facility currently under construction at the University of Edinburgh's Easter Bush Veterinary campus.
In 1996, the institute won international fame and sparked ethical debate when Sir Ian Wilmut, Keith Campbell and their colleagues created Dolly the sheep, the first mammal to be cloned from an adult cell. Scientists cloned the ewe by inserting DNA from a single sheep cell into an egg before implanting it in a surrogate mother.
Three years ago, a Roslin team developed genetically modified chickens capable of laying eggs containing proteins needed to make cancer-fighting drugs.
Last year, scientists discovered genetic "brakes" which could slow down or stop diseases such as multiple sclerosis and cancer.
The study discovered that the way specific genes interact with one another is much more complicated than was previously thought.
The institute employs 68 research staff over five scientific divisions, and its current director is Professor David Hume.
Hogging the limelight in Africa
ANIMALS are being genetically modified at the Roslin Institute to increase resistance to disease.
As well as creating pigs with incurable human conditions, the scientists are also trying to modify the creatures so they can survive a virus called African swine flu.
Whereas European pigs – the large, meat-producing variety – quickly die from the disease if introduced to Africa, the African variety, the warthog, is resistant.
But the two breeds are unable to mate to produce a large, meat-producing variety that is resistant to the disease.
So instead the Roslin scientists have identified a gene in the African warthog they believe could be responsible for the resistance.
"If you take one of our large, meat-producing animals and put it into Africa, within 24 hours it (will be infected and] will bleed to death, which limits our ability to genetically bring this large, high-producing animal into sub-Saharan subsistence," said Dr Whitelaw
"The version of the gene the African pigs have, we believe, may be part of the reason they don't die from this virus."
The work is still at an early stage and no pigs have yet been born that are resistant.
Dr Whitelaw believes the public will find the use of genetic modification in order to help animals stave off disease less controversial than modifying pigs so that they suffer from incurable human conditions.
"Many people, I presume, would say that making an animal able to resist an infection is good.
"When we go to India we get a whole string of vaccinations and we wouldn't dare go there without. This is a similar idea."
However, he still believes it raises complex issues.
"But then you go into issues about what impact bringing in that new type of pig would have on the ecosystem and the society, which are quite complex debates."
• Hugh McLachlan; In a situation like this, all we can do is choose the least unpalatable option