Scientists yesterday announced a breakthrough that could transform research into a range of incurable diseases but spark a dramatic increase in the number of monkeys used in experiments. Researchers have developed a technique to create genetically modified monkeys that suffer from human illnesses.
Experimenting on these monkeys, they believe, will advance our understanding and treatment of incurable conditions such as Parkinson's disease and multiple sclerosis. However, the scientific breakthrough has caused consternation among groups opposed to animal experiments because the development will almost certainly lead to a sudden increase in the number of primates used in medical research at a time when there are calls for fewer monkeys to be used in experiments.
The development also raises the prospect that we will be able to apply the technique to humans – another primate. This could help families affected by inherited disorders such Huntington's disease and cystic fibrosis by permenantly eradicating their defective genes from future generations.
The breakthrough was achieved by a team of scientists in Japan led by Erika Sasaki of the Central Institute of Experimental Animals in Kawasaki and Professor Hideyuki Okano of Keio University School of Medicine. Their study, published in the journal Nature, used marmoset monkeys, the smallest member of the primate group.
The "transgenic" monkeys were created by inserting a gene from a jellyfish into their embryos to make them glow under ultraviolet light – a standard test to see if the technique worked. When the monkeys became adults they passed on this transgenic trait to a subsequent generation of offspring. This "proof of principle" suggests that other genes could also be manipulated to create animals that mimic human disorders. This is already possible in mice.
"The expression of an introduced gene was discovered not only in the first generation of common marmosets after introduction, but also in a second. This is the first case ever established in the world than an introduced gene was successfully inherited to the next generation in primates," Professor Okano said.
"Until now, the use of mice and rats has played an important role in life science research of transgenic animals but to conduct research on human illnesses, experiments with primates, animals markedly closer to humans functionally and anatomically than rodents, have become necessary," he said.
The scientists managed to inject the jellyfish gene into 80 marmoset IVF embryos which were transferred into 50 surrogate mothers. Seven animals became pregnant and four of them gave birth to five live babies.
All five offspring were transgenic animals carrying the jellyfish gene, which caused the production of a green fluorescent protein in the skin of the monkeys which made their hands glow under ultraviolet light.
Most importantly, the scientists demonstrated that the jellyfish gene had become incorporated into the reproductive cells of two of the five marmosets – the sperm of a male and the eggs of a female – both of which subsequently produced a second generation of marmosets carrying the transgenic gene.
It is this breakthrough that could now lead to the establishment of breeding colonies of transgenic monkeys that are each specifically engineered with genes that simulate the symptoms of human disorders to allow them to be used as experimental models, just as transgenic mice have been used in their millions over the past 20 years.
"However, in many cases, research results obtained in mice cannot be directly applied to humans because of the many physiological, anatomical and histological difference between mice and humans, which are evolutionarily distinct," Professor Okano said.
"For this reason, research using primates as experimental animals that more closely resemble humans in function and anatomy is required," he said.
The sentiment was echoed by Kieran Breen, director of research and development at the Parkinson's Disease Society. "This is potentially very exciting for the future of research into the cause of Parkinson's. Because non-human primates are much closer to humans than mice genetically, the successful creation of transgenic marmosets means that we will have a new animal model to work with," Dr Breen said.
However, animal welfare organisations yesterday condemned the research on the grounds that it will lead to an increase in the use of primates at a time when many European countries are trying to reduce the numbers used in scientific experiments.
"It is of high scientific and ethical concern that the creation of transgenic marmosets should be hailed as a success. These experiments will only increase the number of non-human primates subjected to experiments around the globe," said Carol Newman of the Dr Hadwen Trust for Humane Research.
The creation of the first transgenic mouse in the 1980s led to an dramatic increase in the use of laboratory mice during the 1990s. In 1990, there were less than 50,000 experiments involving transgenic mice in Britain – a mere 1.5 per cent of the total – but by 2007 the number of transgenic mice used in experiments grew to more than 1.1 million, according to Home Office statistics.
Why are these experiments important to science?
Q. What have the scientists done?
A. They introduced a jellyfish gene into the DNA of marmoset monkeys when they were embryos. When these monkeys became adults they produced offspring that also carried the foreign gene – the first time a "transgenic" primate has produced transgenic offspring.
Q. But haven't scientists already created transgenic monkeys?
A. Yes, in 2001 the world's first transgenic monkey, called Andi, was created using the jellyfish gene. But the gene was not incorporated into his sperm.
Q. Why is it important to pass on transgenic traits to offspring?
A. Scientists want to establish breeding colonies of transgenic monkeys that are each created as biomedical models of human disorders such as Parkinson's disease or diabetes. If the trait is passed on through normal breeding it avoids the enormous expense of creating each transgenic animal from scratch.
Q. Why was the jellyfish gene used?
A. It is purely a "marker" that allows scientists to see quickly whether their technique has worked. The gene from the jellyfish produces a green fluorescent protein that glows under ultraviolet light. By shining UV light on the animals, scientists can immediately see whether they have successfully introduced the foreign gene into the animal.
Q. Is the breakthrough a cause for celebration?
A. It could soon lead to the creation of better and more accurate animal "models" of human disease because monkeys are closer to humans than mice. It means that medical researchers could test new drugs and treatments and gain a better understanding of incurable human disorders. Opponents argue, however, that animals are not a good model of human illnesses, and the research will only lead to more primates being used in experiments.
Q. Are there any other implications of the research?
A. Being able to manipulate the reproductive cells of primates will inevitably raise the question of whether we can do the same – safely – in humans. This "germline" gene therapy is illegal in Britain because it was considered too dangerous. But if it can be shown to be safe in our closest animal relatives, there could be calls to reconsider its use to eliminate inherited conditions permanently from affected families.
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