Hutch News

Why does a cancer center study AIDS?

Dec. 6, 2001
human immunodeficiency virus

Immature viruses and mature, released viruses can be seen in this image of a T-lymphocyte infected with the human immunodeficiency virus (HIV), which causes AIDS.

Image courtesy of Dr. Michael Emerman

Retirement plans, ID cards and cafeteria hours are among the practical logistics new Hutch staff must navigate.

An equal challenge for many, though, is to understand why scientists at a cancer-research center study AIDS and HIV, the virus that causes the disease, said Dr. Karen Peterson, associate for interdisciplinary training.

"I give a talk each month at new-employee orientation to provide a broad overview of what cancer is and what types of research we do," she said. "Often there are people who are puzzled about why we study HIV at the Hutch."

In fact, AIDS is one of several non-malignant diseases with active research programs at the Center, and many more basic-research efforts are seemingly unconnected to human disease at all.

Along with HIV/AIDS, the study of autoimmune diseases, a collection of disorders in which the immune system turns against the body's normal tissue, is a substantial, non-cancer research area at the Hutch.

But AIDS, autoimmune diseases and cancer are truly interconnected illnesses, said Dr. Lee Nelson, an investigator in the Clinical Research Division. Each, she said, is fueled by an improperly functioning immune system.

"You can think of an intact immune system as a triangle," said Nelson, whose own laboratory studies the autoimmune disorder called scleroderma.

"One corner fights infection, an ability that is compromised in individuals with immuno-deficiencies. Another corner must prevent the attack of normal tissue, which could result in autoimmune disease. And the third is to clear the body of abnormal, potentially cancerous cells."

Research strategies from these multiple perspectives often converge to yield insight into the same system, said Dr. Julie Overbaugh, an HIV researcher in the Human Biology Division.

"The best example is how HIV/AIDS research has advanced the field of immunology," she said. "HIV is a virus that causes a severe immunodeficiency. Yet our understanding of how the normal immune system functions has been aided tremendously by studying what happens when the system fails. Looking at negative and positive effects on a single system, we ultimately understand the mechanisms of a pathway."

Studies on multiple aspects of immune-system function reveal many connections between cancer, immunodeficiencies and autoimmune diseases.

Cancer patients, who undergo treatment with radiation and strong drugs, also have compromised immune systems, which is the reasoning behind the bold signs at the Day Campus clinic of the Seattle Cancer Care Alliance that warn sick visitors not to enter the building. It's also the reason the Hutch supports an active infectious-disease program.

For example, many patients who undergo bone-marrow and stem-cell transplantation for leukemia receive total-body irradiation to destroy their own immune system, which will be replaced by healthy donor cells. Until those new cells are established, the patient's weakened immune system can be plagued by a host of infections easily fought off by healthy individuals.

Many such infections are common to AIDS patients, said Dr. Julie McElrath, an investigator in the Clinical Research Division who also heads a Seattle-area HIV vaccine unit.

"An important research interest at the Hutch is infections of the immunocompromised host, which means those with cancer and with immunodeficiency diseases," she said.

There's also a more direct connection between AIDS and cancer. HIV infection confers a high susceptibility to certain forms of cancer, the most well-known being Kaposi's sarcoma, a disease that affects the skin and mucous membranes.

"People with HIV are clearly predisposed to cancer," Overbaugh said. "We need to understand the interaction between the immunocompro-mised state and the development of cancer."

Institutional history provides strong rationale for the Hutch's diverse research programs related to study of the immune system, Nelson said.

"Our institution really began as a transplant center, which means that you're dealing with immunology, infection and complications of treatment," she said.

Nelson's own research on scleroderma may uncover a link between some autoimmune diseases and graft-vs.-host disease, a potentially serious complication of bone-marrow and stem cell transplantation. Both disorders present similar symptoms, including severe skin rashes, and may arise from non-self immune cells that perturb normal immune system function.

Overbaugh noted that the Hutch isn't the only cancer organization that maintains an active AIDS-research program.

"When I was offered the position at the Hutch, the other place I was considering was the National Cancer Institute," she said, "so we're not unique."

She looks at the topic both philosophically and scientifically:

"My view is that if an institution studies only one small subject, the breadth of how people think about scientific problems will be limited."

 

At-times puzzling basic research can yield enormous advances

The Hutchinson Center has built an international reputation as a leader in cancer care and research.

So it's puzzling to some that many hallways in the Center's research buildings are lined with images of yeast, fruit flies and worms.

Yet basic research on these simple creatures, seemingly unrelated to human beings, has afforded enormous advances in understanding of the human body and the development of cancer and other diseases, said Dr. Mark Groudine, director of the Basic Sciences Division.

"One of the best examples is the work of (Dr.) Lee Hartwell, for which he received the 2001 Nobel Prize in physiology or medicine," he said.

More than 30 years ago, Hartwell, now Hutch president and director, decided to use yeast, a simple, single-celled organism, to study the processes that govern how cells divide. What he found in yeast has held true for every more complex life form in which division has been analyzed.

"The implications of Lee's discoveries about the process of cell division have had a profound impact on our understanding of cancer, a disease whose very foundation stems from uncontrolled cell division," Groudine said.

"One of his key findings was the identification of yeast cellular checkpoints, which ensure that a cell's genetic information is intact before it divides. Analogous checkpoints have since been identified in human cells."

Not surprisingly, defects in these checkpoints arise in a variety of human cancers. Hartwell's work thus provides the opportunity to develop new treatments for cancer and other disorders of cell division.

Other examples of how basic research has fueled understanding of human disease abound, Groudine said.

"That's why the Hutch actively nurtures basic research on problems whose immediate applications may not be apparent," he said. "We never know when or where discoveries like those Lee made will arise."

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