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| Scratching The Biotech Surface |
September 11, 2005 |
By Gail Balfour
Designer drugs, tissue regeneration, nanotechnology and genetic profiling. These are the promises of modern biotechnology, and are only the baby steps in what will be a long journey.
A buzzword today, biotechnology can be traced back to at least 1919, when a Hungarian agricultural engineer first coined the phrase to describe a particular fermentation process. The roots of biotech, however, are found at least 6,000 years ago, when the ancient Egyptians used rudimentary methods to make bread and wine from yeast.
What is different today is the level of collaboration between research disciplines, the amount of information being generated and, for the first time, the use of advanced
technology to manage and manipulate this vast amount of data in a cohesive way, said Dr. Jim Friesen, professor emeritus with the Banting and Best Department of Medical
Research at the University of Toronto.
The world of biotechnology involves not just biologists but mathematicians, computer scientists, chemists and statisticians — experts who have a quantitative view of the world.
This is new. Scientific research, until quite recently, was traditionally composed of islands of information where different disciplines (biology and chemistry, for example) stayed within their separate corners, Friesen said. “It was not airtight, there was just not a lot of back and forth.”
POOLING RESOURCES
But in the past five to 10 years this all changed, he said, and the area is enjoying more collaboration than ever before.
“Now, we get people together from scientific disciplines that never even thought of talking to each other in the past.
(Scientific) papers are being published that would have never appeared otherwise.”
Much of the research done lately with gene sequencing, for example, “could not have been done without collaboration” he said. “We have unleashed a flood of information, but (as biologists), we are not equipped to handle it.”
Computer science and computational biology has now become a crucial step in organizing that data, through categorization, data mining, analysis and pattern recognition.
“That analytical part is the key to the future — making sense from all that information,” Friesen said.
This new world of collaboration is not only changing the way people study and conduct research, it has opened the doors to new communities of science.
One such facility is the Terrence Donnelly Centre for Cellular and Bimolecular Research (or Donnelley CCBR for short), which is part of the University of Toronto. Scheduled to open this September, it will be the first scientific facility of its kind in Canada, bringing together researchers from the faculties of medicine, pharmacy, science and applied engineering. Many projects will use bioinformatics and computational biology.
And in keeping with its eclectic nature, the building has been designed to be flexible and generic. “We can change it from a biochemistry lab to an open dance floor in under two hours,” said Friesen, who formerly held the post of co-director of the Donnelley CCBR.
NO MORE SHOTS IN THE DARK
Dr. Shane Climie, the senior vice-president of science strategy for Protana Inc., a Toronto-based biotechnology company specializing in protein identification, interaction mapping and analysis, agreed information technology plays a key role in helping to interpret all the information the biosciences have to offer.
“There is a real need to manage the process, which is inherently difficult, time consuming and challenging in a number of ways,” Climie said.
“When you understand more about the underlying biology, you can make a more rational strategy to help you tackle disease or infection.”
Protana’s main role is in the area of proteomics — the study of the “molecular machinery” of a living organism: proteins.
“Trying to understand and identify the role of specific proteins in disease and to understand how and when those proteins change as a result of disease, or as a result
of drug treatment, is what we are striving for,” Climie said.
“The actual understanding of what happens at the molecular level is, in a lot of cases, somewhat murky. So the ability to actually observe, measure and identify these changes is extremely useful.”
This is particularly important in the drug development process, he added, because ultimately, practitioners want to measure the effect of a drug on the body in real time.
For example, the current treatment for cancer patients is to administer antitumour medications and, after several months, to measure the tumours to see if the drug worked.
But by measuring biomarker proteins instead, in the near future researchers will be able to detect right away whether or not the drug is working, Climie said.
“And that’s extremely important, because it enables you to identify patients who are, or are not, responding to the drug.
Because in some cases (today) you wait six months, nothing happens, then you try another drug.” By this time, the disease may have advanced too far.
Some targeted therapies are already being used in cancer treatment, Climie said. Traditionally cancer drugs are very toxic and kill a lot of healthy cells as well as diseased ones, creating horrible side effects. “But what’s happened over the past five to 10 years is that we are starting to see the emergence of drugs that are much more
targeted — more like rifle shots rather than shotgun blasts.”
NOT ALL FOR ONE
The fact that not all drugs work in all people is another important reason for studying biomarker proteins, said Dr. Tony Brooks, a senior manager in the Life Sciences
Group at PricewaterhouseCoopers LLC in Vancouver. In fact, according to Brooks, 40 to 60 per cent of drugs don’t work well in any given person.
This is where an area of study known as pharmacogenomics, or personalized drugs, is starting to take off.
“Only recently have we mapped the human genome — there is going to be more and more information [that says] if you have this particular sequence to your DNA, for example, you are likely to respond to certain treatments better,” Brooks said.
“Eventually, the patient is going to say ‘I would much rather take a drug that I am 90 per cent sure will work for me, than try three or four or five different drugs and not
know which one is going to work.’”
Brooks predicts that soon drug companies will be required to provide a genetic test at the same time they present a new drug — this will help show who is likely to respond best to that particular substance.
So, how does the recent mapping of the human genome affect drug development?
“We don’t know for sure,” said Dr. John Evans, chair of the board of directors at MARS (Medical and Related Sciences) Discovery District in Toronto, and vicechair of Mississauga, Ont.-based NPSAllelix Biopharmaceuticals, one of the pioneers of biotech in Canada.
“But we believe that if you could ‘type’ the patient processes of how he/she handles a drug, you could peel off those people who would be particularly sensitive to a drug.
Then you could find a sub-population where the drug is safe and highly effective.”
Evans used the arthritis drug Vioxx as an example. It helped millions of people battle painful inflammation, but was pulled from the market recently because of potential cardiac side effects in some people.
“If the drug company could have predicted which patients would have complications from Vioxx treatment — through some genetic profiling — then a very powerful and effective drug could have been preserved,” Evans said.
His company, NPS-Allelix Bio-pharmaceuticals, has been developing a product since 1989 that will be launched later this year. The drug secretes a parathyroid hormone for treating osteoporosis.
It builds up bone matrix and helps build bone, rather than just delay bone loss as other drugs do.
HAVE A HEART
But not only drugs are being developed to fight disease. Medical devices, such as shunts and prosthetics, are starting to take on “smart” characteristics when combined with drugs.
In the short term, this could mean catheters that measure for and treat infections in the urinary tract, for example, said Mark Steedman, director of business development
at Interface Biologics Inc., a Torontobased biotechnology company that designs “smart” implantable medical devices.
“What we are working on is utilizing the body’s own response mechanisms to turn these devices on and off. We do that by taking the drug and manipulating it at a chemical level,” Steedman said.
The drug “blooms” to the surface of the implanted device (made from a polymer) and then can “tag” or influence certain cells to behave in specific ways. It can also be time released or made to respond to the body’s needs.
For example, in diabetes patients, a device could potentially release insulin by sensing the body’s requirements for it — similar to how the pancreas behaves in a healthy person.
“We are not there yet, but that is where the industry is going,” he said.
Currently, the company is researching ways of treating a cardiac condition known as vulnerable plaques. In some people, these plaques in the arteries break down and cause problems in the bloodstream, leading to stroke or even death.
“Imagine if you could have a polymerlike substance that would be injected into the bloodstream. It would seek out these vulnerable plaques...and that is a more elaborate way of dealing with that problem than potentially going in and putting 150 stents (into one patient).”
The company is also researching “tissue scaffolding,” which may eventually be used for tissue regeneration.
“You are taking a biocompatible scaffold (e.g. a polymer), populating it with growth factors and using the body’s own mechanisms to promote healing, which will force the body to grow new tissues (bone for example). You can program the scaffold so that it biodegrades after a certain time,” he said.
“So, can you regrow a heart? There was some talk a while ago that one day we would be able to get a ‘heart in a box.’ While I don’t think that’s unattainable, I think it’s going to take a while to figure it all out.”
WEB BIOTECH
Banting and Best http://www.utoronto.ca/bandbdonnelley
CCBR http://www.ccbr.med.utoronto.ca
MARS http://www.marsdd.com
NPS-Allelix http://www.npsp.com
Protana http://www.protana.com
PwC http://www.pricewaterhousecoopers.ca
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