ILLUSTRATION: TZIGANE

Protecting the people behind the research

SYLVAIN-JACQUES DESJARDINS | According to some experts, Guy Morrissette should be dead right now.

After all, when a cancerous tumour on his pancreas was diagnosed in January '98, two doctors concurred that nothing could be done to save his life. Although an attempt was made to remove his tumour during a high-risk operation, the procedure was aborted as Morrissette lay on the operating table.

After opening up his patient to get a better look at the malignant growth, Morrissette's doctor determined his case was terminal.

"I was stitched shut again and told that I had six months to live," Morrissette, 63, recalls. "It was bad enough to be told that I had cancer, but receiving the news that it couldn't be removed really killed me."

Determined not to give up, however, Morrissette quickly looked for a new doctor and a weapon to fight his death sentence. Fortunately, he found what he needed at the McGill Centre for Translational Research in Cancer.

Located at the Jewish General Hospital, the cutting edge research centre employs a team of researchers from a variety of disciplines -- chemists, pathologists, molecular biologists and others -- to create a host of cancer-fighting treatments and gene therapies.

These remedies, following animal testing, are then tested on human subjects so they can be fine-tuned as quickly as possible to be prescribed to the general patient population or eliminated if they aren't effective.

Also called Phase I drugs, the experimental treatments created and tested at the centre offer patients not only hope, but the opportunity to contribute to the development of drugs that may one day save their lives and those of countless others.

In Morrissette's case, he's testing a new treatment of animal cartilage extract, which destroys the veins that feed cancerous tumours and prevents them from growing. So far, the remedy is working on Morrissette. It's now a year since he began taking two daily doses of the extract and his cancer appears to be in check.

"The tumour isn't growing," says Dr. Gerald Batist, the centre's director, "which is surprising, given that it was expected to."

That Morrissette is still living thanks, perhaps, to his treatment, Batist says, is a good example of why human testing is vital. Indeed, it is often human testing that supplies the conclusive proof that enables researchers to take their medical breakthroughs from the "good idea" stage to a point where people are benefiting from it in the real world.

Employing human subjects for research is hardly exclusive to medicine. Researchers from a variety of disciplines are continuously testing theories on humans to see what makes us tick.

But when tests are conducted on people, it goes without saying that basic human rights need protection.

That's why all Canadian universities, including McGill, have always had, and updated, ethical guidelines concerning human research. Still, different disciplines sometimes had different sets of rules regarding human testing, while research funding bodies had their own distinct guidelines, too.

But not anymore. Since September, all university research on human subjects is now standardized or governed by one set of rules established by the Tri-Council Policy Statement.

It's a set of ethical guidelines for human research developed by Canada's three major funding agencies: the Medical Research Council, the Social Sciences and Humanities Research Council and the Natural Sciences and Engineering Research Council.

Four years in the making, involving extensive consultation with university ethics boards across Canada, the Tri-Council rules on human research were established to protect human rights at all times -- in all types of research.

"If researchers can't comply with the list of Tri-Council regulations, it simply means that they won't obtain funding for their projects," explains Associate Vice Principal (Research) Ian Butler.

So, for the 1,300 researchers who conducted a total of $182 million of research at McGill last year -- not all of it human-related, of course -- the new Tri-Council regulations are now the ethical standard to follow.

Fortunately, adopting the Tri-Council rules has not been a tumultuous affair at McGill; most of the regulations were already in place throughout the University.

The biggest change McGill made to comply with the Tri-Council Policy was to dissolve its previous research ethics boards (REBs), which ensure that research protocol is followed, and create new boards according to Tri-Council specifications.

Unlike the old REBs, the new REBs must accord at least one out of every five seats to a person from outside the McGill community. Three of the five boards were created for the faculties of agricultural and environmental sciences, education and medicine, while the departments of anthropology, economics, geography, political science, sociology and management were grouped together as a fourth board and linguistics, psychology, social work and music were grouped as a fifth. All remaining departments are in the process of joining one of the last two REBs.

The only wrinkle in the Tri-Council regulations, Butler says, is that non-funded research is so far exempt from the rules, which is why McGill is putting forth a motion to press the Tri-Council to regulate all other funded and non-funded research too.

"It's essential that both funded and non-funded research be governed by the same set of rules," he says. "We just can't countenance that people doing non-funded research would be able to do whatever they want."

Having the rules on human research clearly established by the Tri-Council Policy, says human genetics and pediatrics professor Kathleen Glass, a clinical ethicist at the Montreal Children's Hospital and a member of McGill's biomedical ethics unit, "is a great thing because it raises the profile of the importance of ethical research."

By spelling out what is or isn't permitted in human research, Batist adds, the Tri-Council has also given Canadian researchers a written tool to prevent outside parties from persuading them to bend the rules. "We can use the Tri-Council regulations as a weapon and say we must comply with its norms," he says.

Those rules can be exceptionally handy in the emotionally charged environment of cancer care, where some patients would be willing to bend as many rules as it takes to be accepted as study subjects. But since many of the drugs tested at the centre have uncertain benefits, can produce high levels of toxicity or side effects, the Tri-Council allows only patients in relatively good health to volunteer as test subjects; those who are bed-ridden are inadmissible.

As one of about 100 patients in the test centre this year, Morrissette considers himself fortunate that his stable health, despite his tumour, allowed him to take part in the cartilage testing, that he doesn't have to pay for the treatment and that he's regularly informed about the treatment's progress and side effects.

"Happily," he says, "I haven't experienced any side effects from it myself." Keeping subjects like Morrissette informed about what they're involved in, Batist says, is perhaps the most important aspect of the Tri-Council rules. To produce ethical research involving humans, he stresses, "you need transparency. Any concealment crosses the line."

One of the rare times the Tri-Council allows its rules of complete and up-front disclosure to be flexible is in psychological experiments, where disclosing too much information can ruin the outcome of a study.

"The argument there," says psychology professor Mark Baldwin, "is even if you make (subjects) feel momentarily uncomfortable, if you can ensure that by the end of the experiment they feel good about it, then the (discomfort) is appropriate."

But to ensure such research remains ethical, he stresses, "subjects are still informed, in part, about what they'll be doing and must be treated with respect and dignity throughout the entire experiment."

Currently conducting research on self-esteem differences in men and women, Baldwin also notes that because he often recruits students for his studies, he must also make sure that his subjects don't feel "coerced" into taking part. "It's a sensitive issue," he says, "because researchers at McGill can be considered to have power over students."

For fourth year biology major Jonathan Sullivan, taking part in Baldwin's 30-minute study was a way to contribute to the "advancement of knowledge," while making eight dollars between classes.

"As a student I found the process of how experiments are carried out interesting," Sullivan says, noting this was the third time he volunteered as a study subject. "But I have to admit that I probably wouldn't have participated if these studies had not paid."

Psychology professor Debbie Moskowitz, who is currently conducting a study on interpersonal behaviour, admits many people initially volunteer as human subjects as a way of making extra money. But since her studies can last up to several weeks, her subjects end up sticking through the study for more than the minimum wage honorarium.

"A lot of (subjects) say they gained insight and discovered patterns in their behaviour that they didn't know about," she says.

As researchers wait for computers to one day be sophisticated enough to replicate human characteristics for study, Moskowitz says they have no choice but to continue testing on humans. "Research for people has to be done on people."

Batist agrees, adding that while animals are another important part of research, human subjects play the biggest role. "The step of giving medicine from a mouse to a human is a giant one fraught with many risks," he says. "But it's a critical part of (research) and there's no way around it."