By Jason Hagerman

Over the last 20 years, the world has poured billions of dollars and hours into cancer research, plumbing the depths of our DNA in search of a cure. We’ve discovered causes, treatments and ways to diagnose and detect the disease, yet as of right now, the cure remains a mystery, hidden somewhere, many scientists say, in the complex workings of our nuclear DNA. Some experts, however, disagree. Some believe that the key to abolishing cancer lies in the much less studied mitochondrial DNA (mtDNA). Some believe so wholeheartedly that it lies in the mtDNA, they are willing to stake their reputations and livelihood on it. The founders of Thunder Bay’s Genesis Genomics Inc. did just that, and are producing some staggering results. This begs the question: have we been looking in the wrong place?

How cancer works
Cancer starts with mutation in a single cell, usually the result of some environmental factor. According to Genesis, only between one and five per cent of cancer is inherited. Cells aren’t with us our entire lives. Just like skin cells die and migrate out of the body every month or so, so do all other cells in the body. When a cancerous mutation occurs within a cell, that cell will not follow its regular life cycle. It will not perform its function and be discarded, but will persist and multiply, eventually forming a tumour. As a tumour grows, it becomes parasitic, tapping into bodily resources around it to meet its ever-increasing need for nourishment. A tumour will attract blood vessels, essentially entrenching itself within the body like an organ. Like the cells of any other organ in the body, cancer cells can break off and travel through the bloodstream. The difference is, where other cells would die, cancer cells do not. Because of this, it is not rare for a patient with a specific cancer to develop tumours elsewhere in the body, complicating treatment.

“With cancer, one of the things that doesn’t happen is cell death. These cells don’t die, but continue to grow, becoming a tumour,” says Robert Poulter, President and CEO of Genesis Genomics. Cell death, he explains, is a key factor in the world of cancer and the coding for cell death isn’t hidden somewhere in the billions of base pairs in nuclear DNA.

“Mitochondria is responsible for the majority of energy production in a cell,” says Poulter. “It is also responsible for cell death. When something is going wrong in a cell, or it has simply come to the end of its life cycle, the signal comes from the mitochondria to die.”

A new perspective on cancer detection
Among the founders of Genesis Genomics are a few scientists with unique knowledge and experience in mitochondrial DNA and cancer research. Chief Scientific Officer Dr. Ryan Parr began his research career at the University of Utah in the Department of Cellular, Viral, and Molecular Biology. Additionally, as a Senior Research Specialist at the University of Utah Health Sciences Center in the Department of Hematology and Oncology, he worked on the problem of cancer resistance to drug therapy.

Before starting down the entrepreneurial road, Dr. Robert Thayer, was a professor of biomolecular science at Lakehead University in Thunder Bay. Thayer devoted a great deal of time and energy to researching mtDNA mutation associated with aging, skin cancer and prostate cancer. A decade ago, Thayer traveled to England, where a chance introduction put him across the table from Dr. Mark Birch-Machin, an internationally recognized expert in mtDNA and skin cancer. Birch-Machin is a spokesperson for Cancer Research UK, and has been published more than 100 times in scientific journals. As they sat and exchanged ideas, they came to realize that their experience had led them to the same conclusion: the key to cancer was not in nuclear DNA at all.

When Thayer returned to Lakehead, the wheels began turning and in 2001, the University’s first-ever spinoff was created.

Meanwhile, in 2007, Poulter returned to his hometown of Thunder Bay following a business career that had taken him from Ottawa to Toronto, Bangkok, Singapore and Kuala Lumpur. His credentials made him an excellent fit for the newly created position of President and CEO at Genesis Genomics. “It was a match made in heaven,” he says.

Starting a company focused on researching mtDNA in cancer was a risky move, to say the least. As far as the scientific community was concerned, nuclear DNA was the stronghold of cancer. According to the Canadian Cancer Research Alliance, investment in cancer research in Canada was approximately $400 million in 2006, the majority of which was directed specifically to nuclear DNA research.

In fact, according to Poulter, Genesis has invested more money in mitochondrial science in relation to cancer than the entire U.S. government. “Take the U.S. government, for example,” says Poulter. “They have put literally billions of dollars into cancer research, a large percentage of which has been into nuclear DNA research. I’m sure that the science will grow and continue to evolve with nuclear DNA,” says Poulter, “but to see the huge head start that it’s had and the kind of funding it’s had and still not be able to produce the kinds of results that we’ve been able to, gives us great hope and comfort that we’re on the leading path.”

This is not to say that the global effort put into cancer research has been in vain. Thanks to this research, we know that cancer can be treated through surgery, chemotherapy, radiation therapy and immunotherapy. We know that cancer is mostly caused by environmental factors, and that smoking almost always results in cancer. In Canada, we have learned that lung cancer causes 28 per cent (the majority) of cancer deaths in men, followed by colorectal and prostate cancer. We know that, in women, breast cancer is the most prevalent form of cancer, but lung cancer is still the most prolific killer. Research has led the Canadian Cancer Society to estimate that more than 75,000 people will die of cancer in Canada this year, and that the majority of these will be men.

Indeed, much knowledge has come from these years of cancer research in nuclear DNA, but there is still no cure.

“A lot of money has gone into this research and the scientific community has not found a cure. The closest thing we have to a cure is early detection,” says Poulter. Genesis, he says, offers very early detection—the earliest and most reliable out there.

Proving it
“We have a test that’s ready to go to market that utilizes prostate biopsy tissue,” says Poulter. “About 70 per cent of prostate biopsies come back negative. A pathologist will look at it but will be unable to confirm that cancer is there. In many cases that tissue will be abnormal, but cancer will still not be diagnosed. The pathologist knows something is wrong, but can’t call it cancer.”

The test developed by Genesis, he says, shows that the DNA itself has been altered, which is indicative of cancer. “It also has a field effect. We don’t need to find tissue from a particular tumour to be able to diagnose the cancer. We can find tissue from normalappearing cells that could be in the presence of cancer. We can use that information to lock it down and confirm cancer,” he says.

Mitochondria is a particularly good biosensor for cancer because it has an extremely limited ability to repair itself.

“When something’s going wrong, you can see it in the mitochondria long before you’ll see it in the nuclear DNA,” says Poulter.

Eventually, Genesis plans to use its intimate knowledge of mitochondrial DNA to move away from biopsy tissue analysis to the biofluids that are associated with a given disease.

“In the case of prostate cancer, for example, we would utilize urine. Because the mitochondria has this advantage over DNA in that there are thousands in every cell, we won’t need a significant amount of prostate cells to pass through urine for us to capture a significant amount of DNA that we can analyze,” says Poulter. “The intent of this direction of research is that people will end up going in on an annual basis to have urine screened for prostate cancer in a non-invasive way.”

Early detection through biofluids will not be limited to one kind of cancer. Currently, Genesis has development programs underway in prostate cancer, breast cancer, colorectal cancer, melanoma, lung cancer, ovarian cancer, uterine cancer (also known as endometrial cancer), cervical cancer, bladder cancer and testicular cancer.

The Money Trail “We’ve received money from both the federal government and provincial governments,” says Robert Poulter, President and CEO of Genesis Genomics. “NRC provided us funding through IRAP, they’ve provided us with a commitment to grant up to $1.95 million for research. At the same time, the federal government announced an additional $500,000 investment through the Federal Ministry of Economic Development Initiative of Northern Ontario (FedNor), which has also come through for us in the past. In all, the government has committed over $4 million towards our research.” This money accounts for less than half of Genesis’ funding. The majority of its operating money comes from private shareholders, according to Poulter. “More than

“In each of these areas, we’ve made discoveries and filed patents,” says Poulter.

With a total of 15 employees, 12 of which are scientists, developing 10 new products and bringing them to market within 24 months seems like a lot. Generally, small companies such as Genesis are unable to support such aggressive product development. However, Poulter insists, if the right collaborators were available, the research model that Genesis operates on would allow the company to take on even more product development.

“We’ve got capacity here; the constraint we have is bringing collaborators on board that not only want to work with us, but have sufficient patient loads in these disease areas to collect samples at a rate in which we could utilize them,” he says.

Perhaps there are collaborators out there with the qualities necessary to work with Genesis and really test its capacity for product development, and perhaps those collaborators have simply been looking in the wrong place. Thunder Bay isn’t exactly known as a hub for the life sciences. But the community, Poulter says, is growing. Since Genesis was founded in 2001, Thunder Bay has developed the Thunder Bay Regional Health Sciences Centre and a new medical school at Lakehead University produced its first graduating class in May. There is also a burgeoning presence of other small biotechs and a tissue bank, RegenMed, that’s expanding. In 2006, Philips formed a partnership with the Thunder Bay Regional Health Sciences Centre, Lakehead University and Toronto’s Sunnybrook Health Sciences Centre. This became the $44 million Molecular Medicine Research Centre, which hosts state-of-the-art imaging technologies.

With all this activity happening in the area, Thunder Bay and Genesis are both getting attention from a number of sources.

Researchers who work in the area of mtDNA are keeping a close eye on the biotech, expressing certainty that this part of our DNA is implicated in the cancer genesis. Big pharma is also starting to pay attention, citing knowledge of mtDNA’s role in drug toxicity complications. People are not, however, reacting to the fact that research is being done in mtDNA, but rather that there is simply something out there that may make cancer a more manageable disease. The bottom line is not where the research comes from, but what it ends up doing.

“People react because they know mitochondria or they understand the clinical issue in front of them,” says Poulter. “A doctor may be working on diagnosing prostate cancer and see the value of our prostate cancer test. They don’t care that it’s mitochondriaor nuclear-based, they care that it has top performance and can facilitate the management of a patient.”