Of mice and men

Of mice and men

July 1, 2002

Who could have imagined that a small army of mice might one day fight in the war against AIDS? Sound a little far fetched? Not really. It's exactly what experts like Dr. Paul Jolicoeur would like to see happen in the near future.

In fact, Dr. Jolicoeur knows what he's talking about. He has been working with mice for the last 10 years. In collaboration with his research team at the Clinical Research Institute of Montreal (CRIM), he's trying to develop a mouse strain (animal model) that can be infected with the human immunodeficiency virus (HIV). The challenge? To use genetic engineering to develop a strain of mice that has the human genes needed to be infected by HIV, and that will then react to the virus in somewhat the same way that a human would.

There is still no AIDS vaccine. And no animal model for clinical trials of potential vaccines. And yet, many people incorrectly believe that it's possible to live peacefully with AIDS. Even though new therapies have helped people with AIDS live longer and better lives, HIV infection remains a serious problem with many adverse consequences.

Indeed, AIDS is now the biggest killer in Sub-Saharan Africa, and the fourth most lethal virus in the world. And 21 years after the discovery of the virus, AIDS has now become the most devastating virus in the history of humankind. More than 60 million people have been infected since AIDS was first discovered in 1981, including 5 million in 2001 alone.

According to the latest statistics in a December 2001 United Nations report, 40 million people now live with HIV/AIDS. One-third of these people are between the ages of 15 and 24—and they don't even know they carry the virus.

In 2000, Health Canada estimated that some 50,000 Canadians were living with HIV/AIDS—a 24 percent increase from 1996. Health Canada added that about 15,000 Canadians who have been infected with HIV don't yet know that they are HIV-positive. These figures provide the best indication yet that both the AIDS epidemic and the wave of new HIV cases are far from over.

Benefits

Dr. Paul Jolicoeur and his research team have one objective: to develop an animal model of HIV infection. "We would like to be able to take a sample of HIV, use it to infect a mouse, and give it AIDS," he explains in his laboratory at the Clinical Research Institute of Montreal (CRIM). "The reason is that until we are able to inject the HIV virus into an animal so that the virus reproduces and the animal gets the disease (AIDS), we won't be able to test vaccines."

As far as animal models are concerned, Dr. Jolicoeur says that the rhesus monkey is one of the rare "reliable" animal models currently being used in specialized laboratories. However, the AIDS virus in this type of monkey is slightly different from the human strain. Chimpanzees, on the other hand, can be infected with the virus but they are a protected species, they are very expensive, and their reproductive cycle is long—10 to 12 years. Thus, the use of those two models is hardly practical.

That's why the development of a strain of mice that would be receptive to HIV is especially crucial to AIDS research. In fact, the new strain of mice could accelerate the development of effective infrastructure. In turn, the infrastructure would enable researchers to design new treatments for infected individuals—by allowing researchers to test and develop vaccines more quickly and at a lower cost. In addition, the immunology of mice is very established, and the small, experimental animal is inexpensive and easily available.

However, before Dr. Jolicoeur and his team—largely financed by CANVAC can reach their goal, they must first overcome one obstacle. They have to figure out how to "humanize" mice by giving them the missing or specific genes they need before they can be used to test vaccines. Seems simple enough, but it's a job that will require a huge number of genetic manipulations. "It's backbreaking and frustrating work. It might even be the biggest challenge of my scientific career," says Dr. Jolicoeur. "But on the other hand, this type of research is very daring. We've been working with mice for many years, and we've been toying with all kinds of ideas to achieve what we're looking for."

Another thing that Dr. Jolicoeur had on his mind was the infrastructure that he would need to conduct his work. He knew that if he and his team were to succeed in developing a new strain of HIV-susceptible mice, they would have to conduct their research in a Level P3 animal confinement unit a negative pressure biological containment unit from which nothing can escape unless it's filtered and decontaminated. As a result, they will upgrade their laboratory. The Level P3 laboratory —at CRIM will double in size to house new equipment that includes centrifuges, freezers, incubators, vent hoods, and an autoclave to sterilize the cages used by HIV-infected mice. In due course, the research team hopes to be able to supply the new strain of mice to all specialized researchers on the planet.

"The day our project succeeds, there will be a lot of demand for our new strain of mice—since everyone who is attempting to develop or test new vaccines and therapies will want to do so using these mice," says Dr. Jolicoeur. "This could give us several new weapons to track down and defeat HIV."

Partners

Clinical Research Institute of Montreal (CRIM)
The Clinical Research Institute of Montreal is a world-famous biomolecular and biomedical research centre. It focuses its activities on studying disease causes, developing new diagnostic tools and methods, and finding new approaches for prevention and therapy. A not-for-profit organization affiliated with the University of Montreal, the institute has close to 450 staff members working in 27 specialized research units—in areas such as medical chemistry, molecular biology, functional genomics, clinical research, biomedical engineering, and bioethics.

Canadian Network for Vaccines and Immunotherapeutics of Cancer and Chronic Viral Diseases (CANVAC)
CANVAC is the only Canadian network that brings together partners from the private, public, and institutional sectors—all active in the research and development of prophylactic vaccines and immunotherapies to deal with HIV, cancer, and Type C hepatitis.

CANVAC is a Network of Centres of Excellence.

Networks of Centres of Excellence (NCE)
The NCE Program contributes to the development of effective partnerships between the private sector, the public sector, and universities. The goal of the NCEs financed under this program is to improve the quality of life of Canadians.

Industry Canada and the three federal granting agencies—the Canadian Institutes of Health Research (CIHR), the Natural Sciences and Engineering Research Council (NSERC), and the Social Sciences and Humanities Research Council (SSHRC)—all share in the task of financing and administering the NCE Program.