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Winning the Cancer War

Thanks to a revolution in the understanding of cell biology, leading doctors predict that cancer and other killer diseases will be highly treatable in as little as five years. Can you hold on that long?

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On a beautiful winter afternoon in Southern California, Dr. Dennis Slamon, one of the country's premier cancer researchers, is sitting at a picnic table on the UCLA campus. The grounds are quiet, almost deserted for the New Year's break, and Slamon seems as relaxed as someone who runs a major research lab, a network of more than 50 patient centers, and two national cancer-research programs can be. Between bites of tuna salad, he is telling me, warmly and authoritatively, how life works. Life, that is, at the molecular level.

I'd come out to Los Angeles to have a conversation with Slamon that I hoped would make sense of the remarkable progress being made on some of the most intractable diseases -- particularly cancer -- in recent years. Even if you haven't been paying close attention, you've probably noticed that medical news now comes at a fast and furious pace. You've probably also noticed it now comes with a heightened if somewhat vague sense of optimism. Every few days bring fresh headlines about revolutionary treatments, newly discovered drugs, or miraculous cancer breakthroughs.

This, despite the fact that the major killers have barely been slowed. More than half a million Americans continue to die every year from cancer, and another million new cases are diagnosed. Clearly, there is a gap between what's happening in the lab and what's happening in the doctor's office. So in one sense, my question for Slamon was simple: How long do I have to stay disease-free -- two years, five years, ten years? more? -- until whatever I get can be taken care of?

Straightforward, independent, and celebrated for his accomplishments battling breast cancer, Slamon is particularly well equipped to offer this kind of perspective. For more than a decade, he bucked a cancer establishment focused on radiation and chemotherapy to pursue the targeted, gene-based research he passionately believed in.

The result was Herceptin, the first drug to come to the market targeting a specific genetic alteration that plays a role in causing tumors. In addition to saving lives, Herceptin established a new research paradigm and made Slamon one of the avatars of the new age of molecular biology. And even though he's a leading member of the cancer-research establishment, he remains something of a maverick, unafraid to say what he thinks.

"It could mean the end of disease as we know it," says Slamon. "That's both exciting and scary."

What I really wanted from Slamon was an expansion of an irresistible comment he made in casual conversation over veal and clams at Dominick's on Arthur Avenue in the Bronx, several weeks earlier.

"Just as Einstein completely changed the way people look at the physical world, what's happening right now is going to completely change the way people look at the biological world."

There is a palpable sense in the scientific community that we are in the early stages of what will be an extraordinary age of discovery. "Everyone has talked about the last hundred years, with telecommunications and computers, as having been the information age," says Dr. Lance Liotta, pathology chief at the National Cancer Institute. "But the next hundred years will be the age of biology. This is where the next information revolution will be."

At Johns Hopkins, Dr. Bert Vogelstein, perhaps the country's leading research specialist in colon cancer, is similarly buoyant. "When I was in medical school in the seventies, cancer was really a total black box, and we had no understanding of what caused it. That has completely changed. There's been a revolution in understanding cancer at a basic molecular level. And the whole history of medical research is that once a disease is understood, it's only a matter of time until that disease or its effects are ameliorated."

And so, with the warmth of the L.A. sun on his face, Slamon is patiently laying out the newly developed battle plans in the war on cancer. The main target, he says, is the way the body's cells talk to one another, how they communicate through a critical process called signal transduction. This process is to research scientists right now what the Internet is to investors; it's the place where almost all the energy, money, and creative attention is going. Essentially, the goal is to disrupt or somehow alter the lines of communication when they're being used by the disease.

When these lines of communication are working properly, they enable cells to perform their normal functions. When they break down, scientists now know, or when the "wrong" signals are sent, is when problems develop. Though the actual process is stunningly complex, the basic idea is relatively simple: Cells can send signals back and forth, using proteins as the messengers, based on information provided by the genes. (Manipulating this process is protein therapy; not to be confused with gene therapy, in which genes are introduced into the body. The 18-year-old who died in a clinical trial at the University of Pennsylvania was undergoing gene therapy.)

Everyone is taught in high-school biology that when you get a bug like the flu, the cells in the immune system recognize there's a foreign object in your body, and they develop an offense, attacking the invader. But it's understanding precisely how it all happens -- what initiates the signal, where it comes from, what pathways are used, and which proteins and receptors are activated -- that changes everything.


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