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Tuesday, November 11, 2014

The Koyal Group Info Mag: How A Failed Experiment On Rats Sparked A Billion-Dollar Infant-Care Breakthrough

Researchers studying massages on rat pups helped advance the science on neo-natal care for premature babies, and they will be awarded on Thursday for their breakthrough. | Les Stocker via Getty Images

WASHINGTON -- At a research lab at Duke University Department of Pharmacology in 1979, a group of scientists sparked a major breakthrough in infant care from a failed experiment on rats.
At the time, Dr. Saul Schanberg, a neuroscientist and physician, was running tests on just-born rats to measure growth-related markers (enzymes and hormones) in their brains. Together with Dr. Cynthia Kuhn and lab technician Gary Evoniuk, he kept getting weird results. With the rat pups separated from their mothers in order to run the experiments, their growth markers kept registering at low levels.

The team varied the trials. They used an anesthetized mother rat to feed the pups during and after the experimentation, and tried keeping the pups and mother in the same cage but with a divider to see if a lack of pheromones was the problem.

The experiment failed,” Kuhn recalled.

So the team approached it from another angle. Instead of stabilizing the rat pups so they could run tests, they tried to figure out what was wrong with the pups in the first place. From a friend, Kuhn had heard theories that massaging the pups could produce positive results. Evoniuk, meanwhile, had watched mother rats groom their pups by vigorously licking them. He proposed doing essentially the same thing, minus the tongue.
The team began using a wet brush to rub the rat pups at different pressure levels. Eventually, they found the right one, and on cue, the deprivation effect was reversed.

"I said, 'Let’s give it a shot,' and it worked the first time and the second time," recalled Evoniuk. "It was just the touch.”

Though they had no way of knowing it, Schanberg’s team had taken the first step in a process that would see the upending of conventional wisdom when it came to post-natal care. Three and a half decades later, the theories that his team stumbled upon by failure would save an estimated billions of dollars in medical costs and affect countless young parents’ lives.

On Thursday night, the team will be rewarded for its work. A coalition of business, university and scientific organizations will present the Golden Goose Award to them and other researchers with similar successful projects. It is a prize given for the purpose of shining a light on how research with odd-sounding origins (really, massaging rat pups?) can produce groundbreaking results. More broadly, it’s meant to showcase the importance of federally funded scientific research.

The work done by Schanberg’s team is inextricably tied to the support of taxpayers -- not just because the group operated from a grant of approximately $273,000 from the National Institutes of Health. As Kuhn and Evoniuk both argued, the breakthrough they were able to produce never could have happened with a private funding source. The demand for an immediate result or for profit wouldn’t have allowed them to pivot off the initial failure.

“It is not a straight path from point A to point B,” said Evoniuk. “There are all kinds of weird little detours. We were really following a detour from where this work started. The federal funding gave people like Saul the ability to follow their scientific instincts and try to find the answers to interesting questions that popped up.”

As Congress members head back to their districts before the midterm elections, fights over science funding appear to be low on the list of priorities. The two parties are in the midst of an informal truce, having put in place budget caps this past winter. And no one seems particularly eager to disrupt that truce, even if science advocates warn it needs upending.

While NIH's funding increased this year from last year, when sequestration forced an estimated $1.55 billion reduction, it still fell $714 million short of pre-sequestration levels. Adjusted for inflation, it was lower than every year but President George W. Bush's first year in office.

Surveying the climate, the American Academy for Arts & Science released a report this week showing that the United States "has slipped to tenth place" among economically advanced nations in overall research and development investment as a percentage of GDP. For science advocates, it was another sobering cause for alarm. Young researchers, they argue, are leaving the field or country. Projects that could yield tremendous biomedical breakthroughs aren't getting off the ground.

Looming over the Golden Goose awards ceremony is this reality: Would an experiment testing rat-pup massages ever survive this political climate? Would it be admonished as waste by deficit hawks in Congress?

“Researchers massaging rats sounds strange, but oddball science saves lives,” said Rep. Jim Cooper (D-Tenn.), who is participating in the awards ceremony. “In this instance, premature babies got a healthier start. If Congress abandons research funding, we could miss the next unexpected breakthrough.”
NIH funding was certainly critical to the successful research behind rat-pup massages. "Without the NIH none of this would have happened, zero," said Kuhn.

But serendipity also played a role. Not long after he made his discovery, Schanberg was at an NIH study section with Tiffany Field, a psychologist at the University of Miami School of Medicine. Field had also been doing research -- also funded by the NIH -- on massage therapies for prematurely born babies. But she was getting poor results.

"We were just sharing our data, basically," Field recalled of that conversation. "I was telling him we were having trouble getting any positive effects with the preemies. … He talked about how his lab technician had an eureka experiment when he saw his mother's tongue licking the babies."

The conclusion reached was that Field probably wasn't massaging the premature babies hard enough. Instead of applying "moderate pressure" (as Schanberg had been doing) she was applying more of a "soft stroking."

A study done on rats became a study on humans. Field changed up her experiment and began to see results right away. Instead of the discomfort felt from that tickle-like sensation, the moderate pressure had a tonic effect, stimulating receptors. Babies' heart rates slowed down; the preemies seemed more relaxed; they were able to absorb food and gain weight; there was more evidence of growth hormone; an increase in insulin; greater bone density; and greater movement of the GI tract. The magnitude of the finding was enormous.

"We published the data and we actually did a cost-benefit analysis at that point and determined we could save $4.8 billion per year by massaging all the preemies, because of all the significant cost savings for the hospital," Field recalled.

Her conclusion challenged the prevailing sentiment of the time that prematurely born babies should be left in incubators, fed intravenously, and not touched immediately after birth lest they become agitated and potentially harmed. But few people listened.

"The only person who paid attention to it was Hillary Clinton," she recalled, noting that Clinton, who was working on a health care reform initiative as First Lady, expressed interest in the research.

Since then, however, conceptions of post-natal care have changed. Subsequent studies have confirmed Field's findings, though others have questioned whether there is enough research or the proper methodology to draw sweeping conclusions. Nevertheless, whereas few people used massage therapies in the '80s and '90s, as of eight years ago 38 percent of natal care units were using those therapies, said Fields. The method is estimated to save $10,000 per infant -- roughly $4.7 billion a year.

Those involved in the research still marvel that the chain of events started with a failed experiment on rats and turned on a fortuitous meeting between two scientists.

"We didn’t set out to figure out how to improve nursing care," said Kuhn. "But we wound up saving a lot of money and helped babies grow better, their cognitive outcome was better, they got out of the [intensive care units] sooner. … There was no downside."

"One thing led to another," said Evoniuk. "We were just kind of following an interesting question not thinking we were going to change medical practice."

Schanberg won't be around to receive his Golden Goose award Thursday night. He died in 2009, and his granddaughter will accept on his behalf. But those who worked with him say that his research remains a testament to the good results that an inquisitive mind and a respectable funding stream can produce. It's a story that scientists may find uplifting.

But it doesn't necessarily have a happy ending.

In the aftermath of her work with Schanberg, Field continued studying natal care, starting the Touch Research Institute at the University of Miami in 1992 with the help from the NIH and Johnson & Johnson. Her work has been widely cited in medical journals and newspaper articles. But the funding streams have run dry, and now she's faced with the prospect of dramatically narrowing the scope of her lifelong work.

"We are faced with having to close the institute because we don’t have any NIH grants," she said. "It used to be a third of us would get the grants. Now they are funding at something like the seventh percentile."

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