Essential Types of Mice in Short Supply : Lab Fire Taking Toll on Medical Studies
The fire alarm shattered the tranquility of the Jackson Laboratory’s 94-acre campus at about 1 p.m. on May 10, and within five minutes, smoke was pouring out of the lab’s hangar-like production building.
The blaze spread with horrifying speed. By the time the flames were out the next morning, the body count was at least 350,000--fully half the stock of laboratory mice this one-of-a-kind facility supplies to scientists around the world.
“When I picked up the paper and saw that headline, I almost died. We get a standing order of almost a hundred a week,” said Mary Wood of New England Deaconess Hospital, who is trying to come up with ways to help the human body accept transplanted organs.
Wood, however, turned out to be one of the lucky ones. The supply of the type of inbred mice she needs was less affected than some of the other 1,700 strains that Jackson produces.
Extent of Loss Unclear
It is still too early to assess the full effect of the fire, which started from fumes during construction work. No strain of mouse was wiped out. One thing is clear, though: Some medical and scientific research projects across the country are going to see delays--perhaps of many months--until the nonprofit, private laboratory gets back to its full production of 3 million mice a year.
At the Mayo Clinic in Rochester, Minn., for example, researchers were all set to begin testing a promising drug for arthritis this summer. What they lacked was mice of the one strain in which the disease can be induced.
“The project now has to be put on hold because we can’t get those mice any more,” said Chella David, an immunology professor. “The Jackson lab has told me it will be a minimum of six months before they can even think about it.”
A colleague studying multiple sclerosis also needs an exotic strain, David said, and is “scrounging around to see if he can get the mice anywhere else, and so far, we have not found a source in the United States. We understand there might be a source in Europe where we can buy them, but there’s a lot of restrictions on bringing mice from Europe.”
For now, Jackson is not even shipping any of the surviving mice. It will be weeks before the lab can be sure they were not affected by their brief exposure to the atmosphere during the rescue operation.
Jackson will rebuild its inventory by breeding its so-called “foundation stocks,” the ancestors of the lost mice. Officials said they do not believe they will have to tap their other backup source, half a million eight-celled embryos frozen in liquid nitrogen, which could be implanted in surrogate-mother mice. Those reserves were put in place after the last major fire at Jackson, in 1947.
There are other places that breed mice for laboratory research, but most offer only half a dozen strains or so, compared to Jackson Laboratory’s 1,700.
“Other companies are gearing up to take up some of the slack, but the specialized strains--that’s where the problem will be,” said Jesse O. Washington, campus veterinarian at UCLA, who estimated the university’s orders from Jackson at about 10,000 mice a year.
What is just as important, scientists throughout the country say, is that no one else can touch Jackson when it comes to assuring that a lab mouse is healthy and meets exact genetic specifications.
“You know when you buy a mouse from them that you’re getting what you think you’re getting. They are absolutely rigorous about their genetic controls. And many other places--I’ll be honest with you--they may supply you with mice for half the price, but you pay for it in the long run,” said Marylou Oster-Granite, a developmental geneticist at Johns Hopkins, which orders up to 400 mice a week from Jackson.
In building a better mouse it takes a long time--at least 20 mouse generations--and a lot of patience, to be certain that all the mice of any inbred strain have precisely the same genetic makeup. Two strains, C57BL/6J and DBA-27, date back hundreds of generations, to the early 1900s.
Occasionally, a mutation occurs in breeding that could prove important to science. In such cases, it often takes seven years for the Jackson Laboratory to develop the new strain.
Mice are uniquely useful in research because they are small, relatively inexpensive (Jackson’s prices range from about $3 to $100 per animal) and their genetic makeup closely resembles that of humans.
AIDS Research Furthered
Jackson, working with Stanford University and other centers, last year implanted a human immune system into a mouse that had no immunities of its own. Until then, there was no animal in which the deadly acquired immune deficiency syndrome, or AIDS, could be precisely reproduced.
Generations of inbreeding leave various strains susceptible to certain diseases, which is exactly what scientists need but also means the strains are incredibly fragile. In some areas at Jackson, humans must go through three pressurized chambers, shower and change their clothes before they are allowed to enter the room with the mice.
Other facilities have offered Jackson space for breeding, but their quality control is not good enough for reproducing some strains.
Frantic scientists have been calling the Institute of Laboratory Animal Resources in Washington for help.
“The phone has not stopped ringing with people trying to find animals that used to be available at Jackson,” the institute’s senior program officer, Dorothy Greenhouse, said. “We can’t get anything else done.”
Some researchers have been desperate enough to try breeding mice in their own labs, and are scurrying to find mates for what mice they already have. For many strains, however, breeding is far from a simple match-making proposition, Greenhouse said. One of the strains most in demand, for example, is the New Zealand Black, which develops an auto-immune disease similar to systemic lupus erythematosus, a debilitating rheumatic affliction related to arthritis.
“The problem is that they’re difficult to breed because the female mice have a nasty habit of eating their young,” Greenhouse said. “There are ways around it, but unless you know the tricks of the trade, you have difficulty getting a colony established.”
Dr. Kenneth Paigen, a Berkeley genetics professor who will become Jackson’s director on July 1, said in an interview Saturday that the laboratory’s insurance probably will be inadequate to cover a reconstruction and modernization project that will cost tens of millions of dollars. He is determined, he added, that it not drain resources from the Nobel Prize-winning research done at Jackson.
He plans to tap private sources, such as the biotechnology and pharmaceutical companies that use Jackson mice, and other potential donors. Paigen added that Maine’s congressional delegation is working to see if some federal help is available.
Paradoxically, one of the projects affected by the Jackson fire was research being done by Paigen’s wife, Beverly Paigen, who is senior research biochemist at Oakland Children’s Hospital. She has a three-year, $1-million grant to study the relationship of dairy fat in the diet to heart disease.
Jackson is the largest employer in this picturesque tourist village on Frenchman Bay. It had about 500 employees and has already had to lay off 60 of them. Spokeswoman Barbara K. Trevett said further layoffs are expected.
Paigen said that one of his chief concerns will be making certain the facility is rebuilt so that it will not again be susceptible to a sweeping fire.
“The impact on the national medical research is greater than even we would have guessed,” he said. “This is never going to happen again, period.”
Karen Tumulty reported from Bar Harbor and Charles Hirshberg reported from New York.
