Shutdown Imperils Costly Lab Mice, Years Of Research
The government shutdown is likely to mean an early death for thousands of mice used in research on diseases such as diabetes, cancer and Alzheimer's.
Federal research centers including the National Institutes of Health will have to kill some mice to avoid overcrowding, researchers say. Others will die because it is impossible to maintain certain lines of genetically altered mice without constant monitoring by scientists. And most federal scientists have been banned from their own labs since Oct. 1.
"I'm sure it's chaos at the NIH for anyone doing mouse experiments," says Roger Reeves, a researcher at Johns Hopkins University in Baltimore who uses hundreds of so-called transgenic mice in his work on Down syndrome.
NIH officials say they aren't doing media interviews. So Reeves and other scientists at Johns Hopkins agreed to talk about what a shutdown would mean for their lab animals and the research these animals make possible.
The loss of so-called transgenic mice, many of which have genes that cause them to develop versions of human diseases, is especially troubling, scientists say. A single animal can cost thousands of dollars to replace, they say. And some cannot be replaced at any cost.
To maintain a colony of transgenic mice, every new pup must have its DNA tested by a highly trained researcher, Reeves says. The animal care staff now in charge of NIH mice would not be able to do the testing, he says. So, once federal scientists knew a shutdown was going to happen, they probably had to choose certain mice to eliminate.
"If I thought we were going to be down for two weeks we certainly would reduce the colony," Reeves says. "If I thought it was going to be a month then I would take a little harder look. And if I thought it would be longer than that then we really would have to take things off the shelf."
By "off the shelf," Reeves means freezing some embryos and killing an entire line of mice. Reviving a line that has been "frozen down" can take months and cost thousands of dollars, he says.
Reeves has seen what a government shutdown can do to research. He was at a government lab in the 1980s when a shutdown forced him to walk away from his experiments with cell cultures. The experiments were ruined, he says. "It was a complete waste."
Shutdowns in the 1980s typically lasted no more than a few days. The current one promises to go on for weeks. And that could be disastrous for researchers, says Carol Greider, a researcher at Hopkins, and a 2009 Nobel Prize winner. "Not being able to breed mice for several weeks could really shut down years' worth of experiments," she says.
The NIH will face another problem with its mice, researchers say: overcrowding. Ordinarily, the NIH keeps more than 300,000 mice on hand. But that number has almost certainly been growing quickly since the shutdown, says Bob Adams, who is in charge of research animals at Johns Hopkins.
"Every 21 days a female mouse can have a litter," which can mean 10 or more pups, he says. "So you can see it's a geometric progression of how many mice you would have to deal with."
The mouse facilities at most research institutions run near capacity, Adams says. And national guidelines for research animals prohibit crowding more mice into the same space, he says.
"We might start moving animals around to facilities where we have some room," Adams says. "But at some point we would probably have to start euthanizing animals."
It's not clear how much of that has already occurred at NIH. One reason is that federal researchers had been keeping fewer mice than usual because of budget cuts from sequestration.
In response to questions about mice at the NIH, a spokesperson provided a written statement saying that institute directors are "developing approaches to manage the population of animals so as not to delay experiments further after the shutdown has ended and taking into consideration facility constraints during the shutdown."
Managing the population of NIH mice won't be easy, Adams says. The first thing he would do if Hopkins faced a shutdown would be to separate male and female mice, he says. That would require a lot of extra cages. And pregnant females would still be producing new litters for weeks, he says, which would require many more cages.
Within a couple of weeks of a shutdown, Hopkins would run out of room, Adams says. Then he would have to start bringing animals to a machine that includes a stack of airtight chambers.
Mice cages would be placed in the cages and the machine turned on, he says. "It slowly brings up the carbon dioxide levels so they essentially get anesthetized and then they eventually suffocate," he says
Biomedical research often involves killing animals, Adams says. But usually there is a compelling scientific reason.
ROBERT SIEGEL, HOST:
When the shutdown began 10 days ago, many of the nation's most valuable lab mice were left in limbo. They're held in federal biomedical research facilities where scientists had been trying to find new treatments for diseases, like cancer, diabetes and arthritis. Well, now most of those researchers are banned from their labs. And at the National Institutes of Health, outside Washington, D.C., it appears that thousands of rare and costly research mice will be put to death before the scientists return.
NPR's Jon Hamilton has that story.
JON HAMIILTON, BYLINE: The shutdown poses a special problem for mice that have been genetically altered to develop versions of human diseases, from Alzheimer's to epilepsy. Some of these transgenic mice cost thousands of dollars to replace. Others can't be replaced at any cost. NIH officials aren't doing media interviews. So I asked scientists at Johns Hopkins in Baltimore what a shutdown would mean for their research animals.
Roger Reeves uses hundreds of transgenic mice in his work on Downs Syndrome. And he says to maintain the colony every new pup needs to have its DNA tested by the researchers.
ROGER REEVES: If I thought we were going to be down for two weeks, we certainly would reduce the colony. If I thought it was going to be a month, then I would take a little harder look. And if I thought it was going to be longer than that, then we really would have to take things off the shelf.
HAMIILTON: By freezing embryos and killing entire lines of mice.
Reeves has seen what a government shutdown can do to research. He was at a government lab in the 1980s, when a shutdown forced him to walk away from his experiments with cell cultures.
REEVES: Everything done up 'til that point, lost. It was a complete waste, just an utter waste.
HAMIILTON: Shutdowns in the 1980s lasted no more than a couple of days. The current one promises to go on for weeks. And Carol Greider at Hopkins, a Nobel Prize winner, says that would be disastrous.
CAROL GREIDER: Not being able to breed mice for several weeks could really shut down years worth of experiments.
HAMIILTON: Of course, mice breed even when scientists aren't around. And that presents another problem for the NIH, which ordinarily keeps more than 300,000 mice on hand. Bob Adams, who is in charge of research animals at Hopkins, says that number is probably growing quickly.
BOB ADAMS: Every 21 days a female mouse can have a litter.
HAMIILTON: And how many in a litter?
ADAMS: That varies but it can be a lot, like 10. So you can see it's a geometric progression of how many mice you would have to deal with.
HAMIILTON: Adams says most research institutions don't have much space for extra mice.
ADAMS: We might start moving animals around to facilities where we have some room. But at some point, we would probably have to start euthanizing animals.
HAMIILTON: It's not clear how much of that has already occurred at NIH, where the mouse census had been down a bit because of cuts from sequestration. In an email, an NIH spokesperson said only that institute directors are developing approaches to manage the population.
Adams explains why that will be difficult, as we tour the Hopkins facilities where about 200,000 mice live in stacks of clear plastic cages.
ADAMS: This is what you might call a standard mouse room. It holds about a thousand cages. All the cages receive HEPA filtered air. They receive treated water.
HAMIILTON: Adams says the first thing you do in a shutdown is try to separate males and females. But that requires a lot of extra cages. And pregnant females would still produce new litters, requiring more cages. Adams says within a couple of weeks, they would run out of room. Then, he would have to start bringing animals here, to a stack of air-tight chambers.
ADAMS: We turn the machine on. It slowly brings up the carbon monoxide levels, so they essentially get anesthetized and then they eventually suffocate.
HAMIILTON: Adams says biomedical research often involves killing animals. But usually, he says, there's a better reason.
Jon Hamilton, NPR News. Transcript provided by NPR, Copyright NPR.