Animal experimentation at its worst

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<<< The researchers subjected the mice to stimuli that cause either

short-term or long-term pain. They heated the animals' tails, poked

their foot pads with stiff fibers and injected their paws with

irritating solutions. Then they used molecular and neurological tests

to see how the animals' brains responded and tracked the animals'

behavior -- measuring, for example, how long they licked the site of

injury.

 

Those tests indicated that, compared with normal mice, Doogie mice are

equally sensitive to short-term pain. But chronic inflammatory pain,

such as that caused by the injected irritants, lasts significantly

longer in Doogie mice. >>>

 

http://www.washingtonpost.com/wp-dyn/articles/A58827-2001Jan28.html

 

Study: Rodents' Higher IQ May Come at Painful Price

 

By Rick Weiss

Washington Post Staff Writer

Monday, January 29, 2001 ; Page A02

 

It hurts to be smart.

 

That's one conclusion from the latest study of so-called Doogie mice --

" smart " rodents that are genetically engineered to have enhanced memory

and learning skills. Along with those extra IQ points, researchers have

found, comes an added sensitivity to some kinds of pain.

 

The new work offers a sobering lesson about the difficulty of enhancing

certain brain functions without simultaneously taking a toll on others.

It also may temper whatever momentum there is to engineering genetic

enhancements into people.

 

" Beware what you ask for, " said James L. McGaugh, a neuroscientist at

the University of California at Irvine. " And when you get it, look

carefully and see what else you got. "

 

Doogie mice, named after the precocious television character Doogie

Howser, MD, made a big splash when they were introduced to the world

in September 1999. Having been endowed with extra copies of a gene

involved in memory formation, the animals outperformed their normal

counterparts on a variety of tasks.

 

They were better at recognizing objects they had seen before,

remembered painful experiences longer, recalled with greater accuracy

the location of submerged platforms in milky water and were better at

" unlearning " old associations that were no longer true.

 

Some scientists sniffed at the suggestion that the mice were

particularly brainy, noting that intelligence is much more than a

collection of four or five mental skills. Nonetheless, the work was

surprising because it was the first to show that by adding a few extra

copies of a single gene to an embryo, researchers improve an animal's

performance on a range of memory and learning tasks. Some suggested

that drugs designed to mimic the gene's effects might help Alzheimer's

patients or even make sharp people sharper.

 

The new work hints that it won't be that easy.

 

Min Zhou and his colleagues at Washington University School of Medicine

in St. Louis assessed how Doogie mice responded to tissue damage

and inflammation. They suspected that sensations of pain caused by

those types of injury may be controlled by the same " NR2B receptor "

that

Doogie mice are overendowed with and that gives the animals their

superior memories.

 

NR2B receptors are proteins that act as " coincidence detectors " in the

brain. They recognize, for example, when a certain sound is linked to

the arrival of food and help consolidate such coincidences into learned

associations.

 

The researchers subjected the mice to stimuli that cause either

short-term or long-term pain. They heated the animals' tails, poked

their foot pads with stiff fibers and injected their paws with

irritating solutions. Then they used molecular and neurological tests

to see how the animals' brains responded and tracked the animals'

behavior -- measuring, for example, how long they licked the site of

injury.

 

Those tests indicated that, compared with normal mice, Doogie mice are

equally sensitive to short-term pain. But chronic inflammatory pain,

such as that caused by the injected irritants, lasts significantly

longer in Doogie mice.

 

" Our results suggest that a genetic manipulation confering enhanced

cognitive abilities may also provide unintended traits, such as

increased susceptibility to persistent pain, " the team reports in

today's issue of the journal Nature Neuroscience.

 

Joe Tsien, the Princeton scientist who led the creation of Doogie mice,

said he wasn't convinced the mice feel more pain. The molecular,

physiological and behavioral responses that Zhou's team observed in the

mice could be caused by those mice having enhanced memories of the

painful experience, he said, not enhanced pain itself.

 

" The worst thing would be to say smarter mice are more miserable, "

Tsien said.

 

Other scientists conceded it's difficult to know what mice are

experiencing because they cannot talk. Even in people, the physical and

cognitive components of pain are deeply integrated. Still, several

scientists said, the new study offers strong substantiation that a

Doogie mouse's pain is real.

 

" This is very convincing evidence " that the mice have prolonged chronic

pain responses, said McGaugh, who directs U.C. Irvine's center for the

neurobiology of learning and memory. Moreover, he said, the finding

makes sense. " Most of our brain regions are multipurpose. These things

are all intertwined. "

 

Indeed, others said, evolution rewards creatures that find more than

one use for things, especially things as useful as a neural coincidence

detector.

 

" When nature finds an effective mechanism, it's used and reused, " said

Ira Black, chairman of neuroscience and cell biology at the Robert Wood

Johnson Medical School in Piscataway, N.J.

 

That's why so many drugs have unwanted side effects, and the same will

probably prove true for new drugs that may someday take aim at NR2B,

Black said. People who try to make smarter babies with NR2B genes

or boost their own memory with NR2B drugs may have to accept some

chronic pain. And those who seek to kill their pain with NR2B-blocking

drugs may have to accept cognitive side effects.

 

" You can't have it both ways, " Black said.

 

 

 

 

 

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