Dealing with the details of death

by Tim Lougheed

DEATH HAS NO REASON TO BE PROUD AROUND THE LIKES of Dr. David Park. This researcher with the Neurosciences Program of the Ottawa Health Research Institute, which is affiliated with the University of Ottawa, is the latest recipient of the Young Researcher award, an honour that owes much to his efforts to keep death at bay.

As a molecular biologist, Park is interested in the factors that cause cells to die in a prescribed manner. This process, called apoptosis, started to become the focus of widespread research efforts about a decade ago, when the underlying biochemical mechanisms responsible for cell death were being formally identified.

Through apoptosis, different proteins appear to keep the number of dying cells in balance with the number of new ones being born, normally maintaining a healthy equilibrium within the body. This observation led to speculation that a malfunctioning of these same proteins might be responsible for the kind of uncontrolled cell proliferation found in cancerous tumors, as well as uncontrolled cell death seen in diseases such as Parkinson’s or Alzheimer’s disease. Investigators such as Park see a better understanding of apoptosis as the key to developing medical treatments that deal with the root causes of such ailments.

Park’s research deals specifically with the signaling mechanisms cells use in apoptosis. Having pinned down some of the key molecules that make up these mechanisms, he was among the first to show the therapeutic potential of suppressing enzymes known as cyclin-dependent kinase (CDKs). These enzymes normally control cell proliferation, but are abnormally activated in non-dividing brain cells with catastrophic consequences.

Inhibiting CDKs, he found, can prevent the death of brain cells during a stroke, minimizing the crippling or even fatal damage caused by these devastating cardiovascular events. Because Park has pointed so clearly to the basis for a drug that might be given to stroke patients, his efforts have been an integral part of the Canadian Stroke Network, a federal research network established three years ago with $29 million in support from various public and private sources. Headquartered at the University, this organization has brought together 145 people at 24 universities, 22 private companies and 39 government and non-governmental agencies.

Such solid funding for medical and scientific research was absent throughout much of the 1990s. Park, born in Korea and raised in the United States, was completing postdoctoral work at Columbia University until 1998, and he did not think Canada would be the next stop for his career. Nevertheless, he found in Ottawa the critical mass of expertise in apoptosis that drew him to the University.

Since then, Park’s fascination with apoptosis has never waned.


“Death be not proud, though some have called thee
Mighty and dreadfull, for, thou art not soe,
For, those, whom thou think’st, thou dost overthrow,
Die not, poore death, nor yet canst thou kill mee.”

John Donne (1572–1631), Holy Sonnet


“If you can understand death, you understand life,” he says, noting that death — once regarded as a simple negation of life — is revealing itself to contain a much more subtle and complex set of physiological steps. “The complexity of the issue is what appeals to me. Once you understand that there is complexity, you can more accurately approach the problem. It’s a tremendous challenge. If it were easy, we’d be finished already.”

And being “finished”, he adds, would mean the advent of a therapeutic strategy employing apoptosis. That goal has not yet been realized, but Park concedes that the field has matured significantly since he first began working in it. Some of the early excitement over the discovery of “suicide genes”, along with the implications of learning how those genes work, has given way to a much more orderly analysis of intricate biochemical activity.

Rapid progress in genomics has only added new dimensions to this work. The techniques for assessing genetic activity have become ever faster and more comprehensive, even since Park was completing his graduate work. Yet he insists that these daunting volumes of information must ultimately be interpreted through the same longstanding scientific principles that have been in use for decades.

“Genomics is a valuable tool,” says Park. “But it is only one tool in an arsenal of approaches we have to work with.”

A significant portion of such research initiatives features costly investments in people and equipment. Moreover, as this work aims at well-defined goals such as developing a pharmaceutical agent for a particular purpose, setbacks and outright failures are more likely to occur. But given the increasing incidence of problems such as stroke in an aging Canadian population, renewed pressure falls on the promise associated with research like Park’s to develop therapies to cope with this looming health threat. His scientific curiosity would urge him on in any instance, but this push for practical results can tax his scientific patience.

“It’s frustrating, sometimes,” he admits. “You want to jump right to the end.”