KEY POINTS:
When Bruce Baguley flashes the cross-section of a tumour on his computer screen you begin to grasp the terrible beauty of his challenge. "The cancer's the grey stuff," says the professor, unwinding to his lanky 1.85m and leaning over his desk until his springy white hair almost brushes the monitor.
He points out the components of a tangle of elements that look like a mix of knitting wool, sponge rubber and fancy soap and there, right in the middle, is the chain of ruby-red blood cells that are the key to Baguley's big success.
"Yes, it's complex, and it's also dynamic, changing all the time."
The sheer confusion of cancer - hundreds of different types, each made up of thousands of mutated cells that invade the body in different ways - makes for difficult science.
This solid tumour on the screen illustrates why finding a single knockout drug is as unlikely as discovering the Holy Grail. And why, after 60-plus years, the world's best brains, partnered with its richest drug companies, are still searching for a cure for the most advanced cancers.
As he explains in his soft and measured voice, since those first ferocious chemotherapies of the 1970s that clobbered healthy cells so hard that the process actually killed many patients, progress has been brutally slow. "We still have such a long way to go."
For the first third of his career Baguley concentrated on drugs that targeted the DNA in cancer cells. For the last two thirds, he and his team at the Auckland Cancer Society Research Centre have expanded research into many other types of chemotherapy, including drugs that affect the cancer's blood supply.
Their achievements, in world research terms, has been outstanding. As Baguley says with pride, this 80-strong laboratory on the edge of the world has brought eight drugs to clinical trial - "more than any lab I know of, except the US National Cancer Institute and possibly Cancer Research United Kingdom which has a whole network of labs".
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Most important, for this story, is the Auckland Research Centre's greatest discovery so far.
Known as DMXAA, the new drug developed by Baguley and his colleague, Professor Bill Denny, works in a different way than previous treatments. Instead of attacking mutated cancer cells it attacks the blood vessels that supply the tumour's nutrients.
Results from phase II trials into lung, prostate and ovarian cancers have been promising.
Even better, because of the way the drug works in combination with other therapies, it could be effective on all solid tumours including the most lethal and difficult to treat.
So what makes the Auckland Cancer Society Research Unit so successful? As evidenced by his winning of the Royal Society's Sir Charles Hercus Medal in molecular and cellular sciences and technologies earlier this month and the Peter Gluckman medal for outstanding research endeavours (with Denny) last week, the answer is arguably Baguley.
For the past 38 years Baguley has worked doggedly to improve the chances of cancer sufferers.
It has been an all-consuming career. "You're either in boots and all or you're out."
He talks about how he would have liked to get fitter than the once-a-week tennis matches and 3km walk to and from his Remuera home allow. He would have liked to travel more, to add a fourth language to his fluent German and French that clicks in after a couple of glasses of wine. And more time to practise the cello, which he took up when he was 36 and now plays in the Auckland Symphony Orchestra and in a second, smaller, orchestra in Parnell.
But when you watch him peer down the microscope at a mass of brilliant pink cancer cells which his scientists are bombarding with new chemotherapy, and his blue eyes spark and his long face breaks into a smile, you realise he is blessed.
Here is a man who loves the science, enjoys the patients - and most of all revels in the chance to put the two together. As he says, "we have a direct line to the donors".
Baguley's life is anything but glamorous. His office at the Medical School is pokey and worn. Boring blue carpet, lopsided pictures, a few blue jellybeans in a specimen bottle, rows and rows of medical volumes, a stack of taped-up cartons containing a decade of material from Tertiary Education Commission meetings.
In the three floors above, his staff of 80 scientists and 20 aspiring PhD students are crammed into battered offices, corridors and labs, working on new anti-cancer drugs.
Up the road is the Cancer Society's Domain Lodge, where families can stay in peace with the patients having treatment. Across Park Rd is Auckland Hospital's team of oncologists and wards where patients are providing their cells for research, and the laboratory's drugs-in-progress are being administered and evaluated in real time.
For the past few months Baguley has been working seven-day weeks.
It is the grant season, when directors of all research institutions have to make their cases for funding. As he says grimly, while his secretary and visitors talk outside, "this is the gruelling part of the job".
At 65, the father of three and grandfather of two, who favours stovepipe pants and blue shirts that match his eyes, has a career that paralleled the discovery of DNA and the science of molecular biology.
If the family genes run true he will follow that progress for decades yet. His father died at 92, his mother will turn 100 in January.
His older brother, David, works on earthquake detection at Geonuclear Sciences and his sister, Diane, who originally trained in medicine, works in international quality assessment and with Oxfam.
It all started when Baguley's white hair was brown and Dick Matthews, a talented plant virologist who had worked at Cambridge, England, in the emerging field of DNA and molecular biology, gave a talk at Auckland University.
"He explained how one molecule gave rise to two molecules," Baguley says. "No one knew that before."
By the time Baguley finished his PhD in 1966, he was married to a teacher, Megan, and studying the molecules that allow the connection between DNA segments and protein sequences. "We were ahead of the textbooks. It was an exciting time."
Next came a research fellowship at an academic research unit in Basle, Switzerland. "And one year into that I started studying cancer, specifically what changed the molecules in cancer cells."
His next mentor was Bruce Cain, founding scientist of the Auckland Cancer Society's Research Centre.
By then Baguley was back in Auckland, one of the Research Centre's four scientists, and driven by the desire to develop anti-cancer drugs and work out why some patients responded to a certain chemotherapy and others didn't.
The centre's first breakthrough came in 1978 with the first clinical trials of Amsacrine, an anti-leukemia drug that went on to worldwide use.
Baguley says: "It was Cain's crowning achievement. And proved that a small country could produce a world-class form of chemotherapy."
What it didn't provide was money. "Hardly any at all - it wasn't patented."
Three years later Cain died unexpectedly at 50 and the shattered 40-year-old Baguley stepped up to the challenge.
He instigated a rotating directorship scheme with Denny and set up weekly meetings with the hospital's oncology people. He also took over Cain's drive to keep the Auckland Cancer Society Research Centre on the world cancer research map.
Cain had already developed partnerships with international drug companies, and Baguley travelled to Australia, America and Europe, swapping information and telling and selling the New Zealand story.
Always his main drive was to keep the science in New Zealand. "We thought we should be able to extend the work of the lab to the patient," he says.
"If new drugs were being developed, why didn't we do the testing here rather than letting overseas people do them?"
Over the next 25 years there were several trials, a few triumphs, and the inevitable disappointments:
* Auckland's methods for growing cancer cells in culture, then testing them against various forms of chemotherapy in the lab, was picked up and adopted by Washington's highly regarded Cancer Institute, which tests thousands of drugs.
* In 1986 another drug, Ansulcrine, funded by Parke-Davis, was tested in phases I and II at Auckland Hospital, giving the Research Centre experience in setting ground rules for early trials.
* The Auckland Research Centre was invited to join the clinical trials committee of Cancer Research UK, whose scientists were impressed by Baguley's case for another Auckland-initiated drug, known as DACA. Cancer Research UK is a world authority on trials of anti-cancer drugs. At the time New Zealand was the only non-British member, in itself a breakthrough that gave the Auckland Cancer Research Centre not only international standing but access to Cancer Research UK's rigorous assessment methods.
* DACA was dropped after phase II trials.
* Ansulcrine stopped after phase II trials when Parke-Davis funding was withdrawn. But by then Baguley had already stumbled over the drug that was to become the pinnacle of his career.
"I was talking to a chemist who oversaw all new drugs coming into the testing programme," he says. "He told me about a new drug from France that was quite different from what we'd seen. We got a sample and our research team tested it in the lab here.
"They found it had these properties unlike anything we'd seen before."
What their studies did show was that the drug worked on the normal cells in the tumour rather than on the cancer cells.
One of the centre's chemists made up a slightly different version. "I tested it and that was active as well." As Baguley says, "That's the essence of what goes on in a lab ... you start with one interesting compound and you try to make better ones."
Many experiments, investigations and MRI scans later, the centre's scientists unlocked the secret of the new drug: it targeted and cut off - or at least compromised - the over-activated capillaries that supply blood to the tumour.
Named DMXAA, it became the first drug of its type in a class of anti-vascular drugs.
Although Cancer Research UK approved a trial in Britain, the New Zealand research team had to find money for the local arm of the trial.
Once again Baguley, with his soft, persuasive voice and all-pervading passion, convinced the Auckland Cancer Society to came to the rescue and fund a phase I trial. "Which means that basically we're treating a range of people who don't have any other option - we're using the generosity of cancer patients because it might help someone later on. They're the heroes of this type of research."
"Are they hoping for a miracle?"
"There's always that feeling."
Today, while several other drugs have come, and most gone, DMXAA has gone through its clinical paces.
Last year Antisoma, a British- based biopharmaceutical company that develops "novel products for the treatment of cancer" took over the drug, funding international phase II trials for lung, prostate and ovarian cancer. Auckland scored small trials for ovarian and lung cancer.
Once again, DMXAA proved effective, offering a median survival of 14 months for lung-cancer patients treated with standard chemotherapy plus DMXAA, compared with 8.8 months for those on standard chemotherapy.
Early indications for the yet-unfinished ovarian and prostate cancer trials also look good. For a new cancer drug this is an extremely promising performance. DMXAA will now proceed to stage III trials.
How long has it taken to get to this stage?
"About 20 years."
Twenty years?
"Yes," Bruce Baguley says, drawling the word out, giving himself time to think, as he has for the past three hours. "From the time we started in the mid-80s. There were so many unknowns. That's the fascination of a new drug like this."
Baguley talks with passion and pride about the work of his team. As he says, every cancer is - like the pads on our thumbs - unique to just one person. And the task of designing drugs to attack and kill those cancers is complicated - and endlessly fascinating. It also makes DMXAA, which targets the body's own cells, a genius solution.
For Baguley it is all about patients - particularly the hundreds who have willingly offered cells from their murderous melanomas - brain tumours, ovarian, lung and breast cancers - for testing new drugs, knowing that the chance it will give them even a few more days would be a miracle.
Most of them are now dead. Others perilously ill. And yet they keep on doing it as Baguley and his team hunch over their microscopes and keep their sights fixed on success.
"There's a sense of wonder about biology - learning how normal cells work, how cancer cells work, the relationships going on at microscopic level - it's almost a privilege having learned enough to appreciate it," he says.
On the other hand, "the more you get into the area the more complicated it becomes until you realise that, as a human being, you cannot understand it all, you're visualising something you can never see."
Is it hard keeping yourself going with all the disappointments?
Baguley nods: "So many ideas you have are no good, yet you have to keep on having them. Using different approaches, trying to understand what's going on."
Your dream?
"As far as science is concerned, to contribute to a quantum change in cancer treatment. It's probably a lot to ask.
"The other thing I feel is that, as a country, we need to believe in our ability. In terms of drug development we're well ahead of any other academic group I know of."
Then at 5pm, rain or shine, there he is swinging his small, soft briefcase, a tall, figure sauntering alongside his tiny lab manager, Eileen Marshall. It's when she gets on the train the scientist strides it out for the last couple of kilometres home, keeping himself fit for his God-given task: making sense of cancer's terrible beauty.
Cutting edge of research
To celebrate 50 years of cancer research at the Auckland Cancer Society Research Centre there will be a public information day tomorrow to give the public the chance to see the centre's clinical and scientific work.
It runs from 10am to 2.30pm at the University of Auckland Medical School Cafe, 85 Park Rd, Grafton.
Speakers include:
10am: Professor Lynnette Ferguson; cancer and nutrition.
10.30am: Dr Graeme Finlay; understanding cancer cells.
11am: Dr Michael Hay; discovering a new drug.
11.30am: Dr Adam Patterson; fighting fire with fire - designer viruses for cancer therapy.
Noon: Professor Bill Denny; drug development in a small country - getting a new drug to the clinic.
1pm: Professor Bruce Baguley; The road to individualised cancer therapy.
1.30pm: Dr Michael Jameson; understanding clinical trials.
2pm: Dr Mark McKeage; improved patient outcomes, the result of 50 years of chemotherapy research.
Monday and Tuesday are taken up by an international cancer research symposium.
Long road to perfecting a drug
* Pre-trial phase
Mainly in the laboratory, to establish that a prospective drug is "active" and has some effect on tumour cells.
Cost: 10 to 20 years of research.
* Phase I trial
Tested on volunteer patients, most in the palliative stage of illness. You're looking at how a drug can affect cancer cells rather than normal cells, the best dose to use, and looking in particular for side-effects - and you're also hoping to see some signs of response.
Estimated cost: $1 million.
* Phase II trial
Tested on a larger number of patients (minimum 70) usually in three or more different countries. Patients are divided into two groups. The first is given the trial drug, the second the best available treatment. Patients are monitored rigorously for response over several months, if not years (in the DMXAA trial patients were followed for the course of their lives).
Estimated cost: $10 million.
* Phase III trial
Involves 1000 patients in several different hospitals throughout the world. Once again, the trial is randomised and continues for several years.
Cost: $100 million.
The cost of testing a drug in New Zealand is about half of the cost in the United States.
* The New Zealand Herald / Cancer Society Christmas Appeal
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