by SHARON PROCTOR, PHD
PhotoIllustrations by Martin Krzwinski

In the 18th and 19th centuries cancer was a rare disease. Today it hits one in three people. Why the difference? The answer is we now live longer.

Cancer is mainly a disease of older people. In centuries past, people often died young or in their prime from diseases such as tuberculosis, diphtheria, whooping cough, and other illnesses. But we've conquered all of those with vaccinations and antibiotics. We now live into our seventies, eighties, and even nineties. Some of us live to 100.

Unfortunately, as we age we increase our chances of getting some form of cancer. The prescribed treatment is surgery, radiation and/or chemotherapy, all of which can be ineffective and produce serious side effects. But now a revolutionary anti-cancer weapon is
emerging – the modern supercomputer. At the forefront of this approach is Steven Jones (MSc'94), professor of Molecular Biology and Biochemistry at SFU, and associate director of the BC Cancer Agency's Genome Sciences Centre.

What is cancer? "The cells in our skin, liver, and other tissues are constantly replenishing themselves," explains Jones. "They normally die and get replaced by new cells produced by cell division. Cancer is uncontrolled cell division. The cells never stop dividing." It turns out that essentially all cancers are caused by genetic mutations. In other words, the hereditary material – DNA – becomes altered and turns normal cells into cancer cells.

Steven Jones is identifying these DNA changes so future treatments can target them specifically. And he's using the latest supercomputer technologies at the BC Cancer Research Centre in Vancouver. In some ways, he's "fighting fire with fire."

The fact is DNA itself is a powerful supercomputer. Every cell in our body contains a vast library of hereditary information, all stored in its DNA (short for deoxyribonucleic acid). This DNA contains a complete set of blueprints, orders, and instructions for defining, creating, and maintaining our bodies. It's the body's supervisor, choreographer, regulator, scheduler, enforcer, and controller. It directs our development from fertilized egg to adult, and ensures that our body cells and organs cooperate with each other. It determines the size, shape, structure, and function of our bones, liver, skin, heart, eyes, brain, and other body parts. The sum total of all the information in our DNA is a "genome."

As it happens, the DNA in our cells can outperform the most powerful computers in the world in computing ability, speed, miniaturization, and the amount of data it can store. That's why researchers at IBM and other labs are developing computers based on synthetic DNA. Imagine fitting 10 trillion DNA molecules into the space of one cubic centimetre. You now have a computer that can store 10 trillion bytes of data and do 10 trillion calculations simultaneously. The problem with the DNA in human beings is that our bodies can't always protect it from harm.

Cancer results when certain genes are damaged. Hereditary information is stored in those parts of our DNA called genes. Each gene performs a specific task in the cell. And within each cell, groups of genes initiate and guide chemical reactions, called biochemical pathways. Unfortunately one or more genes will occasionally become altered due to external causes (e.g., cigarette smoke, too much sunshine, toxins) or mistakes in cell division.

It takes several mutations to turn a normal cell into a cancer cell. The genes most often implicated are (1) those that regulate cell division, (2) those that repair damaged genes, and (3) those responsible for turning stem cells into skin cells, muscle cells, and liver and other organ cells. Fortunately for us, most mutations occur in non-gene DNA. Still, it takes only one cell with the right combination of mutations to create a cancer. That's one single cell among the trillions of cells in our body.
Based on this knowledge, many researchers are starting to speculate on how we'll describe cancer in the future. "Classically we've always described a cancer type by the tissue it's in," explains Jones. "So we speak of prostate cancer, liver cancer, skin cancer, bone cancer, and so on. Now we know that each cancer is caused by specific DNA mutations. It's quite possible that at least some cancers arising independently in different organs are caused by damage to identical or related genes.
"We discovered one example in our own laboratory. After analyzing the biochemical-pathway changes that occur in a rare cancer of the tongue, we learned that other researchers had found similar changes in a kidney cancer (renal cell carcinoma)."

The problem with current cancer therapies is that cancer cells are human cells. Thus, any drug or radiation dose that targets cancer cells will also negatively affect normal ones. Radiation fatally damages the DNA in every cell it hits. That said, modern radiation therapy has become amazingly precise in targeting only the cancerous cells. Chemotherapy, on the other hand, kills rapidly dividing cells. Their high metabolic rate makes them especially vulnerable.

"Imagine a car being pursued by police, barrelling along a highway at 140 kilometres per hour," suggests Jones. "That car will be much more sensitive to a pothole than a car going just 50 kilometres per hour." Regrettably there are normal body cells that also divide rapidly, which causes the uncomfortable side effects. What we need are cancer treatments that affect only cancer cells, without damaging any other cells in the patient.

That's the goal Steven Jones and his team have set. "First we need to determine precisely which genes are involved in a given cancer, and to understand all the sub-types of that cancer. That means obtaining a lot of samples of each cancer type, then analyzing the DNA of each sample individually – which is what we're doing now. I'm hoping we'll find the genes commonly implicated in the 10 or 20 most common cancers.

"With further research, we may find different genes that cumulatively affect specific biochemical pathways. Once we know all this, the way is cleared to create drugs that attack only the altered genes or their biochemical pathway. Maybe these approaches won't provide a cure, since cancer has a way of gaining resistance to whatever drugs are given over time. But with an arsenal of different approaches, we can perhaps turn cancer into a relatively harmless chronic condition."

The whole field of genetics and DNA now is vastly computerized. "The Cancer Research Centre has the largest supercomputer in B.C.," says Jones. Indeed, if you were to tour the heart of this system, you'd see individual computers, all stacked like bricks from floor to ceiling, row after row. There are, in fact, over 6,000 CPUs (central processing units) here. Everywhere tiny red lights blink, indicating that the computers are hard at work analyzing, describing, storing, and comparing the genetic information in DNA samples.

Steven Jones and his team are taking full advantage of this powerful tool. In fact, they've greatly improved the computational software used to screen, analyze, and compare DNA samples and genomes. The result is proving useful in a wide range of studies.

"Besides studying cancer, we've done a lot of work on the gene activity within the pancreas and the genetics of diabetes," Jones says. "We've studied HIV, SARS, and illnesses caused by defective genes. We've also analyzed the salmon genome with collaborators at SFU, and we've even extended our expertise to B.C.'s forests. Last year we published the gene sequence of the blue stain fungus. The mountain pine beetle stores this fungus in its mouth and injects it into trees. This stops tree sap from flowing out and resisting the beetle's assault. Together, beetle and fungus have destroyed millions of trees in B.C. forests. We're presently analyzing the mountain pine beetle's DNA."

Steven Jones is a major player in the cancer research community. The best scientific advances arise when scientists from different labs and disciplines cooperate with each other and exchange their research findings. Jones is a perfect example. In addition to working at SFU and the Cancer Research Centre, he's also involved in cancer research programs at UBC as well as international consortia.

So how did Jones end up doing cancer research? After all, he could have been a lawyer, or a physicist, or something else. "I grew up on a sheep farm in Wales in the U.K.," he explains. "I was always interested in farm animals, the different breeds, selective breeding. This attracted me to genetics, inheritance, and DNA."

At age 18 he read Richard Dawkins's book The Selfish Gene. "I was hooked!" He went on to earn a BSc in biochemistry at the University of Bristol, an MSc in genetics at SFU, and a PhD in bioinformatics at the Sanger Institute in Cambridge. When asked what career path he'd have followed had he not pursued this one, he smiles and says, "I would have become a veterinarian!" aq

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