In 2006, Iowa researchers created mice susceptible to coronaviruses. Now, scientists around the world are using them to study COVID-19.


UI scientists could have demanded top dollar and a licensing deal. But they and UI leaders agreed to ship the mice for free. “It was obvious that was the right thing to do,” Dr. Stanley Perlman said.


Several thousand descendants of an Iowa family are giving scientists around the world a head start in the race to find a coronavirus treatment or vaccine.


The family is a special strain of mice, developed more than a decade ago by University of Iowa scientists researching SARS, a disease caused by a coronavirus like the one now spreading COVID-19.


Most mice are nearly useless for testing possible coronavirus treatments because they aren’t seriously sickened by the viruses. But Iowa researchers inserted a human gene into their mice in 2006, making them more susceptible.


A prominent mouse-breeding lab in Maine is now breeding thousands of copies of the Iowa mice. The lab started sending shipments of mice to research teams around the globe this month.


“We’ve got hundreds of people signed up at this point to get their hands on these animals,” said Cat Lutz, a neuroscientist who leads a “mouse repository” at the Jackson Laboratory in Maine. Lutz’s program is a worldwide leader in developing and distributing specialized mice for medical research. It offers access to more than 8,500 strains of them.


Lutz said the University of Iowa’s mouse line, developed by a team led by professors Stanley Perlman and Paul McCray, appears to be the best one anyone has developed for studying coronaviruses.


The Iowa scientists could have demanded top dollar and a licensing agreement, and negotiations could have dragged on for weeks, Lutz said. Instead, they shipped most of what they had to the Maine lab — for free.


When the COVID-19 pandemic first started to spread last winter, Lutz thought her team might have to develop such a mouse from scratch. In early February, she was poring through scientific literature for ideas on how to do so. She came across a 2007 paper in the Journal of Virology that showed a University of Iowa team had already done the work.


The paper's authors included Perlman, a UI virology professor and physician. Perlman had studied the coronavirus disease SARS, which flared up in Asia in 2003 and spread to several other countries, including the United States. SARS killed more than 700 people before fading away after several months.


Many other researchers quickly lost interest in SARS after it flared out, Lutz said. But the Iowa team persisted, and their work included developing mice that could be easily infected with the SARS virus.


In their 2007 paper, Perlman and his partners explained why they had continued their quest: “Although SARS has not recurred in human populations to a significant extent since 2003, the potential severity of such a recurrence has spurred interest in developing an animal model for the human disease.”


Now, as Lutz read the paper in early 2020, the recurrence had been unleashed on the world. Lutz realized the Iowa team had done critical scientific spadework to counter the new scourge.


“I thought, ‘Stanley Perlman is my hero,’ ” Lutz recalled with a laugh.


'We didn't want anyone to have to wait around'


Lutz had never met Perlman, but she immediately contacted him and asked about his team’s mice. He told her the Iowa researchers no longer had any of the animals alive, but they’d stored sperm from the mice in a freezer.


The sperm could be used to fertilize mouse eggs in a lab dish. The eggs could then be implanted into female mice. Just three weeks later, each doe would give birth to several mouse pups that would be susceptible to coronaviruses. Just six weeks after that, those pups would be mature enough to breed to create another generation. And so on.


Lutz asked if she could have some of the material from the Iowans’ freezer. He immediately agreed.


Within days, the Maine researchers had 18 vials of the Iowa mouse sperm and were using it to impregnate does. Each vial held about 200,000 sperm, Lutz estimated. “We used every drop,” she said.


The resulting mice turned out to be very susceptible to the new coronavirus, which causes COVID-19. By late April, several thousand of the special black mice had been born. They soon would be packed into plastic boxes with airholes, and then shipped by truck or plane to eager researchers in the United States, Europe and elsewhere.


Perlman said in an interview that he and McCray, a UI pulmonologist, never hesitated to share most of their frozen stock with Lutz’s lab. The Maine facility is a respected operation that could quickly breed plenty of mice to go around, he said.


The Iowa City doctors told University of Iowa administrators they didn’t want to try negotiating a payment for their precious material. The administrators agreed.


“It was obvious that was the right thing to do,” Perlman said. “We didn’t want anyone to have to wait around.”


Perlman and McCray kept a couple of vials for their team so they could breed their own copies of the mice and study how coronavirus causes sickness and whether vaccines or medications could affect it.


Iowans have studied coronavirus for years


The Iowans' extended focus on coronavirus brought little public attention until a few months ago. Now, they’re in the spotlight.


Perlman said he’s given up to a half-dozen interviews a day. He’s become a go-to expert for the New York Times, the Washington Post and National Public Radio.


His interest in coronaviruses stems from his decades-long research into multiple sclerosis. Coronaviruses' effects on mice are similar to those caused by the auto-immune disease, he said. He suspects such viruses might be a trigger for multiple sclerosis.


He and McCray had already been studying coronaviruses for years before SARS and COVID-19 started killing people. The partners took their knowledge of how the viruses work and applied it toward creating a mouse that could be affected by it. They did so by inserting a human gene into the single-cell egg of a mouse, using a powerful microscope and a needle less than one-tenth the width of a human hair.


Once inserted into the mouse's genetic code, the human gene would lead the animal to make a specific protein on the outside of certain cells. A coronavirus uses that protein as a docking site, where it latches onto the cell before breaking in and using the cell's machinery to create multiple copies of itself. The viruses then stampede out of the cell, spread to other cells and cause disease.


In labs, the mice are infected with the virus so scientists can see how medication or vaccines affect the disease. The research often includes examining the mice after death.


Medical scientist Zachary Freyberg of the University of Pittsburgh is among the researchers who recently received the first shipments of the mice developed in Iowa and bred in Maine. Freyberg helps lead a team that will use high-tech scanners to watch as coronaviruses attach to cells, replicate inside and break back out.


To block the virus' actions, scientists need a clearer picture of how they work, Freyberg said. "The shocking thing is we really don't understand that — the basics," he said.


His team received 10 of the mice about a week ago and expects to receive 10 more. He agreed with Lutz that researchers like him probably got a head start of several months because the Iowa team had a ready-made mouse model to use in studies.


The Pittsburgh researchers also will evaluate whether a specific vaccine shields against the new coronavirus. Hundreds of possible vaccines and medications could soon be tested this way around the world, to see if they offer protection and whether they cause any dangerous side effects.


Scientists say animal trials are an important step in such research, even though most measures that work in animals don't wind up helping humans. Their bodies' systems are similar, but not identical. "That's why there's no magic bullet," Freyberg said.


Perlman has gained notice for presciently warning after the SARS outbreak that the normally mild cold viruses could again pose a serious threat. "But I never really thought that we'd have a disease like this one," he said last week.


Perlman, 71, didn't weigh in on the debate over whether Iowa is moving too fast to reopen businesses amid continuing illnesses and deaths from COVID-19. But he has no immediate plans to sit down in a restaurant or anywhere else Iowans gather. He knows too much about what the virus can do and how hard it could be to find an effective treatment or vaccine.


"The end game is people are going to have to be careful for a really long time," he said. "I want people to understand that this is no joke."


Tony Leys covers health care for the Register. Reach him at tleys@registermedia.com or (515) 284-8449.