Facing cancer

Lived experience reaffirms the role of animals in life-saving science

Articles on this page are the second of a multi-part series on the use of animals in research. The June edition profiled basic science studies, this edition discusses medical research, and upcoming editions will review animal welfare programs and governance.

 When Martin Kirk came down from the high of hosting a national conference as the newly elected president of the Canadian Association of University Research Administrators last year, he had no idea how low life was about to get.

“I had some flu-like symptoms and the left lymph node on my neck was a little swollen, but I figured it was something I picked up on the plane,” recalls Kirk, director of UBC’s Office of Research Services (ORS).

When his lymph node continued to swell, he went to see his doctor and within 30 minutes, was undergoing Doppler ultrasound to confirm the doctor’s suspicion.

“That was the start of a cascade of horrible events,” says Kirk, who was diagnosed with an aggressive case of non-Hodgkin lymphoma in May 2011 and immediately underwent surgery, followed by chemotherapy. Radiation treatment began shortly after his 50th birthday in September.

“When my doctor told me I had lymphoma, it felt like I was being handed a death sentence with a slight chance of parole,” he says. “The only thing I could think of was my two young boys, who needed a dad.

“I just wanted to survive.”

An estimated 40 per cent of women and 45 per cent of men will experience some form of cancer in their lifetime. Non-Hodgkin lymphoma is the fifth most common cancer. While the survival rate is fair for patients under 60, the odds drop dramatically after age 60.

“There is no upside to being told you have cancer,” says Kirk, “but British Columbia is probably one of the better places to be diagnosed because we have some of the best lymphoma experts right here.”

Kirk knew the caliber of cancer research at UBC, which received approximately $72 million in funding related to cancer research in 2010/11. His office manages approval of research protocols and as director of ORS, Kirk signs, on behalf of the university, research agreements to initiate funding from granting agencies.

He credits Rituximab, a powerful chemo drug used for the treatment of lymphoma, leukemia, transplant rejection and some autoimmune disorders, for saving his life (see sidebar). He was also treated with RapidArc, a targeted radiation therapy, to “zap” the cancer in his neck lymph node while preserving healthy tissue nearby, thus sparing him of potential lifelong side effects from damage to his thyroid and saliva glands.

“I have always believed in the importance of research to civil society,” he says, “and I had an intellectual understanding of the link between research and the best available treatment – and ultimate survivability – of patients.

“I survived as a direct result of research,” says Kirk, who returned to work earlier this year and has been cancer free since January 2012. “My appreciation now is much, much deeper.”

Like all drugs and therapies, Rituximab and RapidArc were required by law to first be tested on animals before proceeding to human clinical trials, and before finally receiving approval as clinical treatments in hospitals.

While advanced computing and imaging technologies have reduced the number of animals used in research, cancer and other complex diseases cannot be studied in a Petri dish or on computers alone. No drug or therapy can be used to treat humans without first being trialed for efficacy and safety on animals.

As an administrator intimately involved in the research process, Kirk says there is no questioning the level of care and respect afforded to animals that are involved in research.

“There are never any shortcuts when it comes to approving animal research at UBC,” says Kirk, who sat on the Canadian Council on Animal Care from 2000 to 2003, and is responsible for post-approval monitoring of animal research protocols at UBC.

“Researchers must provide the best care possible because it’s critical to the integrity of the science, which is ultimately what every researcher is judged on. And good science is the foundation of effective, life-saving treatments.”

Kirk agrees the research community has a responsibility to better communicate why and how research is conducted, especially when it involves the use of animals. Still, he says he’s living proof the work is indispensible.

“There is a necessary cost that comes with developing new knowledge.  But the system we have—which includes peer review of scientific merit of all studies, the fierce competition that awards funding to the best scientists, and multiple safeguards in place to ensure the ethical and humane treatment of animals—is very solid.” (See sidebar)

Kirk says his goal is to ensure the process runs smoothly and effectively at UBC, but “at the end of the day, my number one job is being a dad to my kids.”

Cancer research involving animals

The principles of modern cancer chemotherapy originated from a 1973 study using mice that showed a single malignant cell could divide and eventually form enough cells to kill the host—showing it’s vital to destroy every affected cell, and that the earlier the treatment can begin, the better the chances of survival.

The importance of early treatment has also guided research that resulted in earlier diagnosis of cancer.
Chemotherapy, bone marrow transplants, and newer stem cell and antibody treatments (see Rituximab sidebar at right) for leukemia, non-Hodgkin lymphoma and other cancers of the blood, were also developed through the use of mouse models.

Since the early 2000s, the zebrafish has been used to study the genetic aspects of cancer development and potential treatments. While its genome is only half the length of that of humans, zebrafish’s genetic structure is very similar to that of humans, including genes responsible for human diseases.

In 2003, scientists fused Myc, a gene that plays an important role in human leukemia and lymphoma, to a zebrafish gene that works in lymphoid cells. This fused gene was then tagged with another gene that caused leukemia cells to glow green under fluorescent light, thus enabling observation of the cancer as it progressed. The technique has enabled researchers to monitor thousands of genes for mutations that contribute to the disease and to test anti-cancer agents.

Rituximab: A mighty mouse treatment

Approved in 1997 by the U.S. Food and Drug Administration for use in treatment of Non-Hodgkin lymphoma, Rituximab has since been used to treat leukemia, transplant rejection and some autoimmune disorders characterized by too many or dysfunctional B cells.

Rituximab works much like an antibody, in that it attaches itself to a protein on the surface of B cells called CD20 and “flags” them for the body’s immune system to eliminate. Rituximab is a mix of a mouse antibody that was found to be particularly effective at binding to CD20 and a human antibody that interacts effectively with the human immune system.

Prior to human clinical trials, Rituximab was tested in macaque monkeys, which have a constant level of antibodies like humans do. Researchers found that the number of B cells in the monkey’s bloodstream fell dramatically after administration of the drug—as did in the bone marrow (where B cells are produced) and in the lymph nodes (where B cells are activated). But B cell levels recovered in the weeks following—this is important because B cells are vital to a healthy immune system.

More recently, Rituximab, when used with methotrexate, has been shown to slow the progression of rheumatoid arthritis.

Related topics:

UBC Reports | Vol. 58 | No. 7 | Jul. 4, 2012

Martin Kirk credits RapidArc radiation therapy for zapping his lymphoma while sparing healthy tissue. Courtesy Martin Kirk Photograph

Martin Kirk credits RapidArc radiation therapy for zapping his lymphoma while sparing healthy tissue. Courtesy Martin Kirk Photograph

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Animals in UBC medical research

In 2010, 211,604 animals were involved in scientific research at UBC.

Approximately 27 per cent of the animals were involved in medical studies to shed light on the causes and potential treatments for human or animal diseases and disorders.

Under Canadian law, all potential drugs and treatments must first be tested on animals before human clinical trials are allowed. Approximately one per cent of animals involved in research at UBC were part of this kind of study.

For more information,
visit: www.animalresearch.ubc.ca.

Multiple approvals and safeguards

The animal research process involves a series of steps designed to ensure scientific value, humane care and compliance with regulations.

Funding agency approval

Proposals are first submitted to funding agencies for scrutiny by independent panels of experts. Only if the proposed investigation is deemed to be a significant contribution to scientific knowledge will funding be granted.

Institutional approval

Once approved for funding, UBC’s Animal Care Committee reviews all aspects of the project, including ethics and the use of animals. Researchers must demonstrate animals are necessary to achieve research goals, that all feasible alternatives have been considered, and that the project conforms to 3Rs principles of animal use: replace, reducce and refine. If approved, the Committee issues a compliance certificate and funding is then initiated.

Monitoring and training

UBC veterinarians, members of the Animal Care Committee and senior administrators continuously monitor approved projects to ensure humane care and compliance with regulations. Researchers and lab workers must pass mandatory training in animal care.

Continued review

The Animal Care Committee reviews animal research projects annually. Researchers are also required to submit renewed proposals to the Committee for full protocol review every four years.

Published research

When a project is completed, research findings and methods are published in peer-reviewed scientific journals that can be accessed by other experts in the field and the public.

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