Protein snipers

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McGill Reporter
November 2, 2000 - Volume 33 Number 05
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Protein snipers

The future of medicine is in bypassing symptoms to go straight to the molecular root of the problem, says Dr Alan Bernstein, president of the Canadian Institutes of Health Research.

Photo Dr Alan Bernstein
PHOTO: Claudio Calligaris

Take the example of BCR-ABL, a mutant protein unique to chronic myelogenous leukemia. The protein, which was upending people's lives long before it was discovered, now can end up squarely in the crosshairs of targeted drugs, with little or no side effects.

"Traditional chemotherapy is toxic because it affects not only cancer cells but normal cells as well. But a US drug company has designed a drug which inserts itself into this protein, offsets its activity and kills only CML cells."

The drug thus acts like an expert sniper picking off the enemy, replacing a scattershot approach in which lots of allies get caught in friendly fire.

"This is one of the very first examples of a drug designed to address the underlying molecular pathology of a disease. This is an indication of where we're going in coming years."

Bernstein, delivering the Wilder Penfield Lecture at the Montreal Neurological Institute, highlighted the breakthrough as a success story for genomics, one of the key research areas for the next century. Genomics is concerned with mapping and studying the sequence of genes within the chromosomes of an organism's cells.

"There is roughly a one per cent variation in DNA from one person to the next. That one per cent accounts for 30 million bases of DNA, which determines whether we have brown hair or blond, blue eyes or brown eyes -- and whether we are predisposed to breast cancer, colon cancer or schizophrenia. Understanding these differences and being able to relate them back to disease susceptibility is a huge research area which will only continue to grow."

Bernstein foresees an increasingly specific use of medicine to supplant one-size-fits-all treatments.

"Genomic medicine will be individualized based on our genetic makeup. It will be predictive, specific, based on an accurate molecular diagnosis. This approach will produce a whole new class of drugs or treatment approaches focused on a philosophy of prevention. It means getting the right treatment for the right patient."

Gazing into his crystal ball, Bernstein predicts broader trends emerging out of such technological breakthroughs.

"We will move from disease homogeneity to disease heterogeneity, as treatments become more targeted. We will also move from reactive disease management to proactive disease management. Understanding genetic predisposition will mean that we can step in before there are any overt symptoms of disease."

The CIHR, launched on June 7 of this year, is Canada's newest funding agency. It's also the biggest, taking over the mandate of the old Medical Research Council and expanding it into other areas of health research.

Composed of 13 research institutes, these institutes will be encouraged to create synergy between their respective efforts.

"These are not separate research silos; they are meant to be interacting and intercollating institutes. For example, the mental health institute could initiate a project on high suicide rates among Canada's aboriginals. That project could also involve the aboriginal health institute and the neuroscience institute."

In an interview following his lecture, Bernstein, an internationally known scientist with expertise in cancer, blood cell development and gene therapy, explained how individualistic researchers will be prodded to collaborate.

"You can't herd cats -- researchers are like cats, they like to do their own thing. But they tend to go where the action is, and where the money is. The key is to identify timely and interesting scientific questions and put money on the table to encourage them to work together."

To that end, the CIHR is launching this year the Interdisciplinary Health Research Team Competition, "and the quality and quantity of the response has been amazing." The CIHR will also be organizing specialized conferences, called consensus workshops, in which shared interests could spark collaborative projects.

By learning from and complementing each other, Bernstein hopes "researchers will move from being experts in one area to being experts on a problem."

Breakthroughs in increasingly complex fields today depend more on research teams rather than Einsteins working largely in isolation.

"We need pillars of research excellence -- people who are outstanding molecular biologists, medical anthropologists, health economists, etc. -- but we also need pipelines of excellence, in which these people talk to each other and focus on a problem which transcends each of their own disciplines. I think they will want to do it if they see an advantage in terms of advancing their own research interests."

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