A family of genetically modified monkeys with glowing green feet have been created by Japanese scientists in an experiment that could advance research into diseases such as Parkinson’s and Huntington’s.

Although GM monkeys have been born before, the marmosets are being regarded as a scientific milestone because they are the first to have passed a genetically engineered trait from one generation to the next.

The achievement raises the possibility of colonies of GM monkeys being bred for use in medical research. Scientists avoid experimenting on primates when possible, but they remain the best available animal models for studying many conditions, especially brain disorders and infectious viruses such as HIV.

It may now be possible to breed monkeys with mutations causing them to develop diseases such as Huntington’s and motor neuron disease, enabling scientists to study their progress and to develop treatments.
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The research has raised ethical concerns because it could lead to an increase in the number of experiments on primates. Some research groups said, however, that the use of GM monkeys could reduce the number of animals needed because they provided better models for human disease.

A team led by Erika Sasaki, of Keio University, inserted the green fluorescent protein (GFP) gene into 91 marmoset embryos using a modified virus, and 80 of these were transferred to surrogate mothers.

The experiment led to the birth of five offspring, named Hisui, Wakaba, Banko and twins Kei and Kou. Keikou means “fluorescent” in Japanese. Kou’s sperm was then used to fertilise eggs by IVF, resulting in the birth of two more GM marmosets with skin on the soles of their feet that glows green under ultraviolet light. One survived, but the other died after being bitten by its mother. The research is published in the journal Nature.

“The successful creation of transgenic marmosets provides a new animal model for human disease that has the great advantage of a close genetic relationship with humans,” the researchers wrote.

Gerald Schatten, of the University of Pittsburgh, who led the team that created Andi, the first GM primate, in 2000, and Shoukhrat Mitalipov, of the Oregon National Primate Research Centre, said: “The birth of this transgenic marmoset baby is undoubtedly a milestone. The cumbersome and often frustrating process of making a transgenic animal from scratch need now only occur with founder animals.” They pointed out, though, that marmosets were not as useful as rhesus macaques or baboons for modelling some human diseases.

Kieran Breen, director of research and development at the Parkinson’s Disease Society, said: “This is potentially very exciting for the future of research into the causes of Parkinson’s disease.” Simon Festing, the chief executive of Understanding Animal Research, said: “Ethical evaluation and public engagement are vital to maintain confidence in such research.”

Together, two common pesticides may increase the risk of Parkinson’s disease.
Apr 27, 2009

Costello, S, M Cockburn, J Bronstein, X Zhang and B Ritz. 2009. Parkinson's disease and residential exposure to maneb and paraquat from agricultural applications in the Central Valley of California. American Journal of Epidemiology 169: 919-926.
Synopsis by Jonathan Chevrier, Ph.D.

The risk of Parkinson's disease increases in people who live near farm fields sprayed with a combination of pesticides.

A recent study conducted in California’s Central Valley found that people who lived near fields sprayed with a combination of pesticides used on crops such as potatoes, dry beans and tomatoes had an increased risk of Parkinson’s disease.

This is the first study to evaluate associations between exposure to a combination of pesticides and the risk of Parkinson’s disease.

These results add to the growing literature suggesting that exposure to multiple chemicals may be more harmful than exposure to individual chemicals and contribute to the debate of evaluating chemical safety one at a time rather than in combination.

The cause of Parkinson’s disease is still a mystery to scientists but reports of higher risks of this ailment in farmers and in rural populations have lead some to hypothesize that exposure to pesticide mixtures may be a contributor.

The scientists found that people who live within 500 meters of a field sprayed with the pesticides maneb and paraquat in combination, but not individually, had a 75 percent higher risk of Parkinson’s disease relative to controls. Being exposed to the mixture at a younger age resulted in an even higher risk. Individuals potentially exposed to these pesticides when they were 60 years old or younger were 5 times more likely to be diagnosed with Parkinson’s disease.

These results are predicted by studies which showed that exposing rodents to maneb and paraquat together resulted in reduced motor activity, nerve cell loss and decreased levels the neurotransmitter dopamine in certain areas of the brain as observed in Parkinson's patients. Animal studies also predicted Costello's finding that effects of these pesticides would be more important when exposure occured at a younger age.

Researchers obtained these results after comparing potential exposure to pesticides in 368 people with Parkinson’s diseases and 341 people without living in an agricultural area. Exposure was estimated using land-use maps and data from the California Pesticide Use Report, a program which requires that the precise date, chemical and location of spraying be reported to the State.

However, biological markers, such as pesticide concentrations in urine and blood, were not measured. Other factors associated with living close to certain fields may explain the reported association.

UCLA researchers have provided strong new evidence linking at least some cases of Parkinson's disease to exposure to pesticides. Researchers have suspected for some time that pesticides may cause the neurodegenerative disorder, and experiments in animals have shown that the chemicals, particularly the fungicide maneb and the herbicide paraquat, can cause Parkinson-like symptoms in animals. But proving it in humans has been difficult because of problems in assessing exposure to the agents.

Parkinson's is a disorder of the central nervous system that often impairs the sufferer's motor skills, speech and other functions. It is not fatal of itself, but complications often are. The disease has been recognized since the Middle Ages but became more prevalent in the 20th century. As many as 180 of every 100,000 Americans develop it.

To explore a potential connection to pesticides, epidemiologist Beate Ritz of UCLA and her graduate student Sadie Costello, now at UC Berkeley, studied public records of pesticide applications in California's Central Valley from 1974 to 1999. Every application of pesticides to crops must be registered with the state. Working with Myles Cockburn of USC, they developed a tool to estimate pesticide exposure in areas immediately adjacent to the fields.

They then identified 368 longtime residents who lived within 500 yards of fields where the chemicals had been sprayed and compared them to 341 carefully matched controls who did not live near the fields.

They reported in the current issue of the American Journal of Epidemiology that people who lived next to fields where maneb or paraquat had been sprayed were, on average, about 75% more likely to develop the disease. But those who developed the early-onset form of the disease -- contracting it before the age of 60 -- had double the risk of contracting it if they were exposed to either maneb or paraquat alone and four times the risk if they were exposed to both. In most cases, the exposure occurred years before the onset of the disease. Exposure to other pesticides did not appreciably alter the risk.

"The results confirmed two previous observations from animal studies," Ritz said. "One, that exposure to multiple chemicals may increase the effect of each chemical. That's important, since humans are often exposed to more than one pesticide in the environment. And second, that the timing of the exposure is also important."

-- Thomas H. Maugh II