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Will we ever… eliminate animal experimentation?.

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Arguably one of the most heated debates in science, efforts to reduce the number of animals used in studies face many barriers, says Alla Katsnelson.

One of the most, if not the most, contentious issues in science is the use of animals in research. Scientists experiment on animals for a host of different reasons, including basic research to explore how organisms function, investigating potential treatments for human disease, and safety and quality control testing of drugs, devices and other products. Its proponents point to the long list of medical advances made possible with the help of animal research. Opponents believe it is cruel and meaningless, as observations in animals often do not translate directly to humans.

In 1959, William Russell and Rex Burch proposed their “3Rs” guidelinesfor making the use of animals in scientific research more humane: restrict the use of animals; refine experiments to minimise distress; and replace tests with alternative techniques. Over the course of five decades their guidelines have become widely accepted worldwide, and while the reliability of published reports on the numbers used varies, they do at least provide a snapshot of historical trends. Around 29 million animals per year are currently used in experiments in the US and European Union countries. (Rats and mice make up around 80% of the total.) This is less than half the total in the mid-1970s – a significant drop, but one that has plateaued in the last decade.

“In the late 1980s, people thought animal research was singing its swan song,” says Larry Carbone, a senior veterinarian at the University of California in San Francisco. Fresh out of veterinary school in 1987, Carbone landed a job as an animal vet at Cornell University, in New York State. At that time the numbers of animals being used in experiments and testing was on the decline: the campus was building a new multi-storey biotechnology facility, with just three rooms containing animal breeding and living facilities.

But then came the development of tools that could selectively modify individual genes in mice. This proved to be such a powerful and popular technique that the decreasing trend in animal use ground to a halt.

Now, a raft of novel experimental techniques may help to push numbers down again. Improvements in imaging methods that offer a peek inside the bodies of animals allow scientists to get more and better data from each experiment than before. For example, researchers previously had to cull multiple mice at different stages of tumour development, but now they can non-invasively watch the disease unfold in a single living animal using a fluorescent dye. Similarly, as brain-imaging techniques become more advanced, some questions that are now addressed with experiments in monkeys might be better answered by peering into the human brain. “My prediction is that human volunteers will be able to replace monkeys more and more in the next 10-20 years,” says Carbone.

Meanwhile in vitro advances are also pointing towards reliable alternative methods. One such advance is the ability to re-program human skin cells into a primordial, stem cell-like state. These “induced pluripotent cells” could be converted into any specialised cell in the body, like liver or kidney cells, and these could be generated from people with a particular illness, giving researchers a potent and patient-specific model of that disease in a dish. Lab-on-a-chip technologies – and perhaps one day,lab-grown organs – could also provide increasingly sophisticated ways to identify disease mechanisms or test prospective medicines.

Finding alternatives

Trends also show that some sectors are doing more than others to reduce animal use. Some believe technological advances will one day make animal studies unnecessary, while others argue that “non-living” models will never be capable of reliably replicating all of the uses of laboratory mice and other creatures.

When many people think about animal testing, they imagine rows of rodent cages in a pharmaceutical company lab. But according to data from European Union countries, the pharmaceutical sector uses almost half the number of animals that academic labs do, and animal use in drug development dropped significantly between 2005 and 2008 – the most recent statistics available. There are two reasons for this, says Thomas Hartung, Director of the Center for Alternatives to Animal Testing at Johns Hopkins University, in Baltimore, Maryland. First, drugs are increasingly designed to target specific molecular mechanisms, and these are best identified in culture dishes rather than live animals. Second, conducting experiments in 1,536-well cell culture dishes is vastly less expensive than in animals, so companies are motivated to use alternatives whenever they are available.

In the US and the EU, a drug’s efficacy and safety must be tested in animals before it enters human testing, though a 2010 directive from the EU calls for alternatives to be used when possible. Jan Ottesen, vice president of lab animal science at Danish company Novo Nordisk, which makes insulin and other drugs for diabetes and haemophilia, says his company actively seeks out tests that can replace animal use without compromising patient safety. Novo Nordisk decided 15 years ago to replace animal tests with cell cultures to verify the quality of each batch of drugs before it goes to market. The company had to provide the authorities with data proving that other tests worked just as well. It took until 2011 for the company to complete the switch. 

However, for some types of experiments there are no equivalent non-animal options, says Ottesen. For example, in searching for new drugs that decrease joint pain due to arthritis, you need a model that mimics the human condition. The important thing, he stressed, is to set up the experiment so as to avoid unnecessary pain. For safety and toxicological testing of drugs, he adds, “I cannot see for the foreseeable future how we can completely avoid it. Having said that, all the replacements that can be implemented should be implemented.”

Under pressure

Safety testing of substances other than human and veterinary drugs, such as cosmetics, toiletries, household cleaning products and industrial chemicals might be a different story. Currently, says Hartung, such tests are outdated and inaccurate, with toxicity in rodents predicting problems in humans just 43% of the time. Meanwhile, tens of thousands of these substances have undergone no toxicity testing at all.

Addressing this gap with animal studies alone would be expensive and impractical. An overhaul of chemical safety regulations in the EU calledREACH and a toxicology modernisation initiative led by the US National Institutes of Health, are driving the search for alternatives.

Hartung believes that with enough investment and coordination, animal tests on products in this category can be replaced completely. He is leading the Human Toxome Project, an initiative that aims to map the ways substances disrupt hormones and endanger health, as well as to develop advanced, non-animal lab tests for toxicity testing. It’s slow going, Hartung concedes. “We don’t have human data to compare with, or really high-quality animal data,” he says, adding that this makes it tough to evaluate the quality of the tests.

Meanwhile, almost four in ten animals are used in basic, as opposed to applied, biological research – and this proportion is growing. Sarah Wolfensohn, a veterinary surgeon who heads Seventeen Eighty Nine, a consultancy advising researchers on animal welfare, based in Swindon, UK, says this is in part because a lot of this type of work is carried out in academia where the financial and performance pressures that motivate interest in non-animal-based techniques are weaker than in the commercial sector.

Other factors play a role too, she says. “For example, if a senior professor in academia has spent his entire career developing experimental techniques on monkeys’ brains and young researchers now tell him ‘actually we don’t need to do this, we can do it on a computer’, it undermines his approach.”

But just as important as reducing the numbers of animals used, adds Wolfensohn, is “to make sure they are being used in the best way and that their welfare is maximised, so as to get the best quality results, to make sure they are not wasted.”

Overall, pressure to limit the use of animals in research – either for financial, scientific or moral reasons – is rising. Meanwhile, the use of animals in many areas of life-science research is on the decline, experts note, even if genetic work in mice is still keeping numbers up. “I think this is temporary,” says Andrew Rowan, President and Chief Executive Officer of animal protection group Humane Society International. “I think it is going to start going down again as we improve our technologies.” How soon this might happen is too difficult to tell.

Source: BBC

 

 

 

 

 

Brain scans of rappers shed light on creativity.

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Functional magnetic resonance imaging shows what happens in the brain during improvisation.

Rappers making up rhymes on the fly while in a brain scanner have provided an insight into the creative process.

Freestyle rapping — in which a performer improvises a song by stringing together unrehearsed lyrics — is a highly prized skill in hip hop. But instead of watching a performance in a club, Siyuan Liu and Allen Braun, neuroscientists at the US National Institute on Deafness and Other Communication Disorders in Bethesda, Maryland, and their colleagues had 12 rappers freestyle in a functional magnetic resonance imaging (fMRI) machine.

The artists also recited a set of memorized lyrics chosen by the researchers. By comparing the brain scans from rappers taken during freestyling to those taken during the rote recitation, they were able to see which areas of the brain are used during improvisation. The study is published today in Scientific Reports1.

The results parallel previous imaging studies in which Braun and Charles Limb, a doctor and musician at Johns Hopkins University in Baltimore, Maryland, looked at fMRI scans from jazz musicians2. Both sets of artists showed lower activity in part of their frontal lobes called the dorsolateral prefrontal cortex during improvisation, and increased activity in another area, called the medial prefrontal cortex. The areas that were found to be ‘deactivated’ are associated with regulating other brain functions.

“We think what we see is a relaxation of ‘executive functions’ to allow more natural de-focused attention and uncensored processes to occur that might be the hallmark of creativity,” says Braun.

He adds that this suggestion is “a little bit controversial in the literature”, because some studies have found activation of the dorsolateral prefrontal cortex in creative behaviour. He suggests that the discrepancy might have to do with the tasks chosen to represent creativity. In studies that found activation, the activities — such as those that require recall — may actually be less creative.

“We try to stick with more natural creative processing, and when we do that we see this decrease in the dorsal lateral regions,” says Braun.

Pump down the volume

Rex Jung, a clinical neuropsychologist at the University of New Mexico in Albuquerque, has also studied the link between brain structures and creativity, finding an inverse relationship between the volume of some frontal lobe structures and creativity3. “Some of our results imply this downregulation of the frontal lobes in service of creative cognition. [The latest paper] really appears to pull it all together,” he says. “I’m excited about the findings.”

Jung says that this downregulation is likely to apply in other, non-musical areas of creativity — including science.

The findings also suggest an explanation for why new music might seem to the artist to be created of its own accord. With less involvement by the lateral prefrontal regions of the brain, the performance could seem to its creator to have “occurred outside of conscious awareness”, the authors write.

Michael Eagle, a study co-author who raps under the name Open Mike Eagle, agrees: “That’s kind of the nature of that type of improvisation. Even as people who do it, we’re not 100% sure of where we’re getting improvisation from.”

Liu says that the researchers are now working on problems they were unable to explore with freestylers — such as what happens after the initial burst of creative inspiration.

“We think that the creative process may be divided into two phases,” he says. “The first is the spontaneous improvisatory phase. In this phase you can generate novel ideas. We think there is a second phase, some kind of creative processing [in] revision.”

The researchers would also like to look at how creativity differs between experts and amateurs of a similar artistic ilk to freestylers: poets and storytellers.

Watch the video on youtube.URL: http://www.youtube.com/watch?v=LmreCiyV-Kc&feature=player_embedded

Source: Nature

 

 

 

 

 

Cherries May Prevent Gout Flares.

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Patients with gout were less likely to report acute attacks after 2 days of eating cherries or imbibing cherry extract than during periods after no cherry intake, according to data reported in Arthritis & Rheumatism by Yuqing Zhang, DSci, and colleagues from Boston University School of Medicine in Massachusetts.

Dr. Zhang, who is professor of medicine and epidemiology at Boston University School of Medicine, told Medscape Medical News that cherry intake during a 2-day period was associated with a 35% lower risk for gout attacks and that cherry extract intake was associated with a 45% lower risk.

Risk for gout attacks was reduced by 75% when cherry intake was combined with allopurinol use. Dr. Zhang said, “We found that if subjects took allopurinol alone, it reduced the risk of gout attack by 53%; if subjects took cherry alone, it reduced the risk by 32%; if they took both, the risk of gout attack was reduced by 75%.”

These associations were discovered in a case-crossover study of 633 individuals with physician-diagnosed gout who were prospectively recruited and followed online for 1 year. When a participant reported a gout attack, the researchers asked about the onset date of the gout attack, symptoms and signs, medications, and potential risk factors (including daily intake of cherries and cherry extract) during the 2 days before the attack. Patients served as their own controls, so the same information was assessed for 2-day control periods not associated with gout attacks. A cherry serving was defined as one-half cup or 10 to 12 cherries.

Participants had a mean age of 54 years; 88% were white and 78% were male. Of patients with some form of cherry intake, 35% ate fresh cherries, 2% ingested cherry extract, and 5% consumed both fresh cherry fruit and cherry extract. Researchers documented 1247 gout attacks during the 1-year follow-up period, with 92% occurring in the joint at the base of the big toe.

Factors associated with increased serum uric acid levels, such as increased alcohol consumption and purine intake, or use of diuretics, were associated with increased risk for recurrent gout attacks.

“Our findings indicate that consuming cherries or cherry extract lowers the risk of gout attack,” Dr. Zhang said in a press release. “The gout flare risk continued to decrease with increasing cherry consumption, up to three servings over two days.” Further cherry intake was not associated with additional benefit.

“However, the protective effect of cherry intake persisted after taking into account patients’ sex; body mass (obesity); purine intake; and use of alcohol, diuretics, and antigout medications,” according to the release.

The authors speculate that cherries may decrease serum uric acid levels by increasing glomerular filtration or reducing tubular reabsorption. They also note that cherries and cherry extract contain high levels of anthocyanins, which possess anti-inflammatory properties.

Dr. Zhang told Medscape Medical News, “While our study findings are promising, randomized clinical trials should be conducted to confirm whether cherry products could provide a nonpharmacological preventive option against grout attacks. Until then we would not advocate on the basis of the current findings that individuals who suffer from gout abandon standard therapies and opt for cherry extract products as an alternative.”

In an accompanying editorial, Allan Gelber, MD, from Johns Hopkins University School of Medicine in Baltimore, Maryland, and Daniel Solomon, MD, from Brigham and Women’s Hospital and Harvard University Medical School in Boston, write that the findings are promising but reiterates the need for randomized clinical trials to confirm that consumption of cherry products could prevent gout attacks.

Dr. Gelber told Medscape Medical News, “For the patient who asks his/her doctor ‘Doc, what can I do, myself, to decrease my chance of developing another gout attack, above and beyond the medications you have prescribed for me?’ our response would include that one of the options is dietary modification. Previously, physician recommendations included advocating for moderation in alcohol consumption, weight reduction, and decreasing high-purine foods from the diet…but now there are new data supporting a beneficial role in eating cherries to reduce one’s risk for recurrent gout attacks.”

Dr. Gelber noted that the most definitive support for the recommendation to eat cherries as a strategy to reduce gout risk would come from a randomized clinical trial. “Just as with new medications that come down the pipeline, dietary interventions ought also be subject to the rigor of a clinical trial. Such a study could be undertaken. There is logistical challenge to undertaking such a trial since cherry fruit is broadly available. But, in a controlled setting, such a trial would be feasible,” he said.

Source: Mescape.com