Does Animals Respod To Drugs Like Humans Do

Most potential new drugs fail when they're tested in people. These failures are non just a major disappointment, they sharply drive up the toll of developing new drugs.

A major reason for these failures is that most new drugs are outset tested out in mice, rats or other animals. Oftentimes those fauna studies evidence great promise.

But mice aren't but furry little people, then these studies often lead science astray. Some scientists are now rethinking animal studies to make them more constructive for human health.

When scientists beginning started using animals in research over a century ago, the animals were not regarded equally human stand-ins. Scientists studying rats were initially trying to empathise rats, says Todd Preuss, an anthropologist at the Yerkes National Primate Research Heart at Emory University.

"As this process went on, people stopped seeing them as specialized animals and started seeing them more and more equally prototypical mammals," Preuss says.

But is a rat really a generic mammal? Preuss says emphatically no. But that's how rodents were pitched when they became products sold to scientists.

"It wasn't strictly a fiscal involvement," he says. The sellers "actually believed that y'all could do nigh anything" with these animals. "Y'all could acquire virtually well-nigh any feature of homo organization, you could cure almost whatsoever illness by studying these animals."

That was a dangerous assumption. Rats and humans have been on their ain evolutionary paths for tens of millions of years. We've developed our ain unique features, and and then have the rodents.

So information technology should come as no surprise that a drug that works in a mouse often doesn't work in a person. Withal, Preuss says at that place'southward tremendous momentum to go on using animals as human substitutes. Entire scientific communities are congenital upward around rats, mice and other lab animals.

"Once these communities exist, then you take an infrastructure of cognition: how to enhance the animals, how to go along them healthy," Preuss says. "You have companies that leap up to provide y'all with specialized equipment to report these animals."

The rat holding facility at Hazelton Laboratories in Washington, D.C., in 1967. Fob Photos/Getty Images hide caption

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The rat belongings facility at Hazelton Laboratories in Washington, D.C., in 1967.

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Chances are, people studying the same disease study the same tailor-made strain of creature. Journals and funding agencies actually expect information technology.

"So at that place'southward a whole institution that develops," Preuss says.

And it's hard to interrupt that culture. (Preuss spoke nearly this subject in a 2016 talk at the National Institutes of Health.)

You tin get a glimpse of the scale of this enterprise by passing through one of hundreds of facilities nationwide devoted to the care and feeding of mice. On the Stanford University campus, attendants whorl supply carts through fluorescent-lit hallways and by row after row of doors at an expansive mouse facility.

I'chiliad guided through the labyrinth by Joseph Garner, a behavioral scientist at the Stanford University Medical Heart. We go into a windowless room stacked flooring to ceiling with seemingly identical plastic cages full of mice.

The philosophy backside mouse research has been to make everything as uniform as possible, and so results from one facility would exist the same as the identical experiment elsewhere.

Just despite extensive efforts to be consistent, this setup hides a huge amount of variation. Bedding may differ from one facility to the next. So might the diet. Mice answer strongly to private human handlers. Mice too react differently depending on whether their muzzle is up near the fluorescent lights or subconscious downward in the shadows.

Garner and colleagues tried to run identical experiments in six unlike mouse facilities, scattered throughout inquiry centers in Europe. Even using genetically identical mice of the same age, the results varied all over the map.

Garner says scientists shouldn't fifty-fifty exist trying to do experiments this way.

"Imagine you were doing a human drug trial and you said to the FDA, 'OK, I'g going to do this trial in 43-twelvemonth-old white males in i small-scale town in California,'" Garner says — a boondocks where everyone lives in identical ranch homes, with the same monotonous diets and the same thermostat set to the same temperature.

"Which is too cold, and they can't alter it," he goes on. "And oh, they all have the same grandfather!"

The FDA would laugh that off as an insane setup, Garner says.

"But that's exactly what we do in animals. We try to command everything we tin peradventure think of, and every bit a result we acquire absolutely nothing."

Garner argues that enquiry based on mice would be more reliable if information technology were set up more like experiments in humans — recognizing that variation is inevitable, and designing to embrace information technology rather than ignore it. He and his colleagues take recently published a manifesto, urging colleagues in the field to look at animals in this new calorie-free.

"Maybe we need to finish thinking of animals every bit these little hirsuite exam tubes that can exist or even should be controlled," he says. "And perchance instead we should recollect of them as patients."

That could solve some of the problems with animal inquiry, but past no ways all.

Scientists make far too many assumptions almost the underlying biology of disease when creating animal models of those illnesses, says Gregory Petsko, who studies Alzheimer'south disease and other neurological disorders at the Weill Cornell Medical Schoolhouse.

"It's probably only when you lot get to effort your treatments in people that you lot're really going to accept any thought how right those assumptions were," Petsko says.

In his field, the assumptions are often poor, or downright misleading. And Petsko says this mindset has been counterproductive. Scientists in his field accept "been led astray for many years past relying then heavily on beast models," he says.

For many years that was simply the best that science could do, Petsko says. So he doesn't fault his colleagues for trying.

"What I am saying is at some bespeak you have to cutting your losses. You lot accept to say, 'OK, this took us as far as it could take us, quite some fourth dimension ago.'"

For neurological diseases, Petsko says, scientists might acquire more than from studying human cells than whole animals. Animals are yet useful for studying the safe of potential new treatments, but across that, he says, don't count on them.

Preuss at Emory agrees that using animals every bit models of disease is a big reason that many results in biomedical research aren't readily reproducible. "I call back that we take ways to resolve that, though."

How? "You have to think outside of the model box," he says. Mice and rats aren't simplified humans. Scientists should cease thinking they are.

But Preuss says scientists can still learn a lot about biology and disease by studying animals — for example, by comparing how humans and other animals differ, or where they share common traits. Those can reveal a lot nigh biology without assuming that what's true in a rat is likely truthful in a human.

"Scientists demand to break out of a culture that is hampering progress," Preuss says. That's tough to do right now, in a world where science funding is on the chopping cake. Many scientists are reluctant to have a risk that could backlash. But the upside could benefit us all, in the form of a better agreement of disease, and effective new drugs.

Richard Harris did some of the reporting for this story while researching his volume Rigor Mortis: How Sloppy Science Creates Worthless Cures, Crushes Hope, and Wastes Billions. You tin can contact him at rharris@npr.org.

Source: https://www.npr.org/sections/health-shots/2017/04/10/522775456/drugs-that-work-in-mice-often-fail-when-tried-in-people

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