The man behind the cure

Discovering a drug to treat a type of leukemia has made Dr. Brian Druker the face of the fight against cancer

By PETER KORN Issue date: Tue, Oct 4, 2005 The Tribune
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Everybody wants a piece of Dr. Brian Druker. That's what happens when you take on cancer and emerge as the hero of a scientific movement.

One day you're spending 90 hours a week in the lab, your eye practically stuck to the microscope. Then skip forward and you're treating leukemia patients in a clinic, watching men and women about to die get up and start dancing before the week is out. Before you know it, the world is knocking at your door, arms wide open.

If you have cancer, of course, you want the advice of the Portland man who discovered Gleevec, the closest thing yet to a cure for the disease, even though the drug is only effective on a few types of cancer.

If you're a scientist, you'd like a consult from the colleague who may have found the path that leads to scientific bliss. Leukemia survivor groups? Who better as a guest speaker than the doctor who gives them hope. Congress invited Druker to testify on the future of cancer research.

And don't forget medical students and university doctoral candidates. It all adds up to 20 to 25 speaking engagements a year. Everybody needs a little inspiration. "He's become the face of the fight against cancer," says his wife, Alexandra, who sees what her husband's discovery has meant to the world of cancer, yes, but also to Brian Druker and his Portland employer.

While Druker makes no money directly off his groundbreaking discovery, it has brought tens of millions of dollars in new funding to Oregon Health & Science University and job offers to Druker that he wouldn't have dreamed of 15 years ago.

Let's get this straight. Druker did not invent Gleevec. Chemists working for the pharmaceutical company Novartis had first synthesized the drug in a lab back in the late 1980s. But a use for it had never been found. Until 1998.

That's when Druker found a way to use Gleevec to successfully treat sufferers of chronic myeloid leukemia, a rare form of cancer also known as chronic myegenous leukemia or just CML.

Since then he has used Gleevec on patients with other forms of leukemia, and patients with an otherwise fatal chemotherapy-resistant gastrointestinal cancer. Late-stage cancer patients are almost never cured. Druker?s patients seemingly have been.

But let's back up. Fifteen years ago Druker was an instructor and scientist at Harvard University. He had worked there for six years and in his own words, "I was a nobody." Not quite a nobody: He was listed by the National Institutes of Health among the top 10 percent of scientists in the country. But Harvard had plenty of people ranked in the top 1 percent or 2 percent. "I was told my work there wasn't good enough," he recalls.

But it was at Harvard in 1986 that Druker learned his most important lesson - what he needed to know about himself. On a Saturday afternoon in the lab he began to wonder why he had gone to medical school. He loved lab work; he?d become a scientist. But years had passed since he?d seen an actual patient. And the lab work, though fascinating, was too far removed from the people it was intended to benefit.

Druker stopped being just a scientist that afternoon. He talked to a friend who ran a community oncology clinic in Boston, and shocked the friend when he said he wanted to work there. "I thought you were going to be a lab rat," the friend said.

Druker began to leave the lab one half-day each week to treat cancer patients.

Five frustrating years
In 1993 Druker accepted an offer from Dr. Grover Bagby to work at the new OHSU cancer institute. Within five years Druker's work was turning the world of cancer research on its head.

Druker, 50, stands tall and straight, without the hunched over look of some who spent too many hours poised over a microscope and petri dishes. There?s a plaintive quality to his soft speech, as if he's pleading for the world to understand what he already knows. The problem with being a visionary is that not everybody is capable of seeing the connections you see.

That's why Druker spent five frustrating years before 1998 persuading Novartis to produce enough Gleevec so he could try the drug out on patients with CML in clinical trials. The drug company didn't see the profit potential in a therapy for a disease that struck 5,000 people a year.

Eventually, Druker did prevail in getting Novartis to produce Gleevec for his clinical trials. Druker's dual roles as lab scientist and caring physician were what carried the day.

Nick Lydon was project leader at Novartis, and dealt directly with Druker. He always thought about "How will this benefit the patients?" - Lydon says. "Other researchers around the world were testing Gleevec. But Brian was the most impressive because he clinically translated this."

Lydon says Druker's passion for both his work and his patients made him stand out in a very competitive, sometimes cutthroat world.

"He is an ethical, thoughtful guy who doesn't bull---- you," Lydon says. "He doesn't try and tell you what he doesn't know. He's very focused on helping you make the right decisions."

Working miracles
The results from OHSU arrived more quickly than anybody anticipated. Druker immediately began seeing patients return from being nearly dead. A dietitian from Washington already had chosen a burial plot and was discussing what music she wanted played at her funeral. A month after Gleevec treatment had begun, her disease had all but disappeared.

In fact, Druker's initial patients were selected precisely because they were close to death. With an unproven drug there was the possibility of toxic side effects; the only people a clinic would be allowed to test it on were those with no alternatives.

Doug Jenson was one of those. He refers to himself as No. 13, the 13th patient to receive Gleevec in the first clinical trial. A CML sufferer, "I was so sick I couldn't even walk across the room,?" he says. Today, at 72, the Canby resident lifts weights and works out at the Wilsonville Bally's Total Fitness gym nearly every day.

Alexandra Druker recalls one of her husband's brought-back-from-the-brink patients, a Mormon who told her, "I put Brian right up there after God." So do others: There are entire Web sites created by Druker's patients offering long letters of devotion to his work.

Perhaps the miracle was in Druker's vision, perhaps in his persistence. "He saw people dying while waiting for Novartis to invest," Alexandra says. Druker fought for his ideas, and he was right. But the field of battle only shifts, it never disappears. There are always patients who relapse, always new cancers to target.

Bridging two worlds
To understand Brian Druker you have to understand the two worlds in which he works.

The oncologist's world is filled with frustration and sometimes despair. Despite modern medicine's advances, just about as many people die from cancer as did decades ago.

Honest oncologists will tell you that they try to prolong life and enhance the quality of life of their patients, but chemotherapy is a crapshoot and radiation of limited use. Caring for people with cancer can take an emotional toll.

The world of the lab scientist requires absolute attention. Cancer cells in petri dishes can be riveting, even all-consuming, and in time they can force the scientist to narrow his focus further and further, knowing the more he attends to those cells, the more successful he is likely to be.

But his colleagues say Druker has the rare ability to work in both worlds and to keep one in mind when he's in the other.

"As a scientist you have a certain amount of passion for your ideas," says Michael Heinrich, an OHSU cancer institute professor who has worked with Druker. "But you have a completely different level of passion when you feel you are advocating for your patients and all the leukemia patients in the world."

When Druker's in the lab waiting for cells to respond to a chemical bath, he is motivated by the knowledge that his patient list is long and filled with people who are dying.

When he's in his office seeing patients, he says, his awareness of their conditions, the frustration he feels in watching them deteriorate, motivates him to get back to the lab, try harder, focus better, to come up with something that can help them.

So many of those "1 percenters" at Harvard, first in line for funding, lacked something Druker did have - compassion. He was never just a lab rat. Druker himself thinks coming to Portland saved his career, not only because of the opportunity the OHSU lab presented, but because it allowed him to escape the "herd mentality" at Harvard that had researchers all pursuing whatever research model was popular at any given moment.

Slowing down
Three years ago Druker, still working 80-hour weeks in the lab, married Alexandra, who had a 4-year-old son from a previous marriage. The two now have a 3-year-old daughter as well.

Druker had gone through a brief first marriage while at Harvard, attending more to the lab than his personal life, and he learned. This time he's the husband who empties the dishwasher early every morning before heading out the door for his daily run to work. And he brings Alexandra tea in bed.

Has success changed Brian Druker? He acknowledges that it has. For one thing, it has made him think in ways he never had to before. "I've always wanted to do something big," he says. "I've done what I set out to do. What do you do when you've accomplished what you set out to do? I keep going."

But Druker has a more philosophical side, maybe the result of his new family. A father now, he can look back at his own father through a different lens.

Druker's dad was a chemist who only took his son to work once. He was a hard-driving man who, when told by his son that he had been accepted into medical school at the University of California at Irvine, asked why the son couldn't get into a better school.

"No matter how good you did there was something you could have done better," Druker says.

Druker's father died shortly before Gleevec's success. He never heard his son hailed as a genius. But the son knows what the father would have said if he had lived that long. "Well, you're probably not going to win a Nobel Prize for that." Or, "But it's not a cure, is it? I still hear him."

Druker says his 80-hour work weeks have been cut nearly in half. Not everybody's so sure. Every night, after dinner and play time with the children, Druker and Alexandra go to bed, where Druker sets up his laptop computer and opens his personal e-mail.

Letters pour in from all over the world. Letters from grateful people alive because of his work. Letters from people who want advice on dealing with their own diseases or their own careers in science.

"He answers them all," Alexandra says. Eighty hours a week down to 40 or 50? "I don't know," Alexandra says. "Not if you include the e-mails."

Hard for a man to even think of slowing down when taking time away from his work can translate into people close to dying who he might save. Druker has made his peace with the dilemma, and whether his softer schedule is 40 hours or 60, the answer lies in all those speeches and testimonies that take him away from the clinic and the lab.

"We need more people (who) can do this," he says. "There are many ways you can measure success in a career, and one of them is in the number of people you train and inspire that can go on to do work more brilliant than what you did."

Followed his own path
Soon, in the new OHSU biomedical research building, he will have more lab scientists working on his projects than ever before. He gets to choose which scientists train under him, and which projects they pursue.

And when Druker heads out to talk to a group of medical students or budding scientists, he often flashes back to when he was a medical student and a teacher asked what course he intended to pursue.

His response at the time was oncology and lab science, his two passions. "You'll be really lucky if you're good at one of those," he was told by the teacher. "You should choose the one you'll be better at."

If Druker had followed that advice, people with chronic myeloid leukemia would be dead now, instead of playing with their grandchildren or working out at the Wilsonville gym. "Don't tell me what I can do and can't do," he says. "Tell me what I need to do to accomplish my goals".

"There's a reason that we pass the baton generation to generation. Fifteen years ago somebody trying to develop a drug like Gleevec was told, "That won't ever work; you're wasting your time." Now the generation coming along looks at Gleevec and says, "Of course that should work." They're not constrained by the chains of the past that say you can't do this, you can't do that. They have new, novel ideas that go beyond anything I could even imagine," he says.

Scientist, oncologist, maybe Brian Druker's greatest role, the one that marks all his work, is that of the translator, the bridge. He bridged the worlds of lab science and clinical oncology. Now he's serving as a bridge between generations, and between those who have faced death and those who have not.

Druker met Alexandra, a journalist, when she was writing a story about him, before his Gleevec success. "One of the toughest questions she asked me was "What do you learn from your patients?" he recalls. "The obvious answer for an oncologist is I've learned to live each day one at a time. The problem is, if I learned that, and did that, I wouldn't have worked so hard and accomplished what I accomplished.

"But what I did learn from my patients, so many of them faced a death sentence. Gleevec comes along, and now all of a sudden they're feeling great and their hope for the future has returned and they tell me stories of this dark cloud lifting from their shoulders. And they're planning for the future again. And I realize, the greatest gift you can give anybody is hope.

Rewards of research system not always direct, immediate
Gleevec will make about $2 billion for the drug company Novartis AG this year. So what about the guy who discovered the drug?

Oregon Health & Science University's Brian Druker doesn't make a penny off his discovery. That's because technically, he didn't discover Gleevec; he discovered a use for it. The drug, known by chemists as ST1571, has been around since the late 1980s.

Here's how the clinical research system works. Large pharmaceutical manufacturers such as Novartis employ thousands of chemists to produce new compounds. Some are distilled from naturally occurring substances. Aspirin, for instance, originally was derived from the bark of a willow tree.

Other compounds are pure invention, the product of chemists playing around with molecules to produce designs they think might be useful. Often, the scientists are looking to invent drugs based on obscure molecular models.

Novartis chemists synthesized ST1571, so Novartis holds the patent on Gleevec.

When Druker was looking for a drug that might work on a defective class of proteins that caused chronic myeloid leukemia, he called a friend at Novartis and asked for a recommendation. Novartis originally sent Druker five or six compounds, Gleevec among them.

Months later Druker had his "Eureka!" with Gleevec, and OHSU had added prestige. But all the money that comes from Gleevec's wide use, now on not only CML but also other cancers, goes to Novartis.

Which isn't to say that Druker and OHSU haven't benefited financially. Maintaining a cancer lab and clinic costs money. But as a research institution, OHSU has its own way of generating revenue. Research institutions get most of their funding from grants. Druker's model for fighting cancer is hot, so if you're a foundation looking to fund cancer research, there's no better place to send your bucks than OHSU. Post-Gleevec, the Howard Hughes Institute committed to fund just about everything having to do with Brian Druker: his $125,000 salary, his research needs, even new equipment in his lab.

Dan Dorsa, vice president of research at OHSU, says the institution has netted tens of millions of dollars in grants as a result of the Gleevec discovery. The OHSU cancer center has had its National Institutes of Health designation as one of the country's elite cancer centers renewed. And that was at least partially due to Druker's breakthroughs.

At its campus on Marquam Hill - otherwise known as Pill Hill - OHSU is completing construction on a new biomedical building. An entire floor, 275,000 square feet, is dedicated to cancer research.

Come January, that's where you'll find Druker's office and lab. Part of the deal is a chemical biology program, something new to OHSU. That's where OHSU chemists will begin synthesizing their own molecular compounds, maybe the next Gleevec among them.

And if OHSU's chemists somehow synthesize a success like Gleevec, OHSU - not the pharmaceutical company - will hold the billion-dollar patent.