Doctors' Need to Suppress Emotion

How would you like to cure cancer? Careful, it's a trick question. You might win a Nobel Prize, along with the gratitude of countless strangers who will owe their lives to you. But you'll need to explain to people along the way that you can't save everyone's life. Some of them might be your friends. Are you prepared for that? It never crossed Mark Davis's mind back in 1996 when he decided to take a crack at the most intractable problem in medicine. He wasn't a doctor or a biologist, but a professor of chemical engineering at Caltech, with a specialty in nanoparticles: assembling molecules into microscopic three-dimensional structures. He also had a wife with breast cancer, who was suffering horribly from the side effects of chemotherapy. You guys at Caltech are so smart, she said one day, why don't you invent something better?

So he did. Immersing himself in the literature, he saw a way to apply his expertise to the problem. Most cancer drugs work by attacking rapidly dividing cells, which include tumors but also much healthy tissue, which is why they make patients sick. So one research goal has been to exploit a unique vulnerability of tumors. Their chaotic growth is fueled by a jury-rigged blood supply whose vessel walls are much more porous than normal. A drug married to a particle of the right size could reach cancer cells but be too large to diffuse into healthy organs—minimizing the side effects, or, to put it another way, allowing a larger dose of chemotherapy without the risk of killing the patient. For the active agent, Davis settled on camptothecin, a potent but quite toxic chemotherapy drug. For the delivery envelope he chose a large polymer based on the starch molecule cyclodextrin, engineered to release its payload of camptothecin gradually, which is how it is most effective, and then to degrade harmlessly. This took him almost 10 years. His wife, meanwhile, recovered—both from cancer and (mostly) from the effects of her conventional treatment.

And then came the hard part, as his drug, dubbed IT-101, went into the first phase of clinical trials, intended to establish a safe dosage. The problem was that it worked almost too well. His very first patient, a young man with pancreatic cancer who was given only about three months to live, is still alive today, more than a year later. Good results were also seen in patients with "massive" lung and kidney tumors, Davis says.

These results are preliminary, but more than good enough for someone who's been given six months to live. As word spread on campus of Davis's work—and, later, after it was discussed on the public-television documentary "Curious"—calls began coming from people desperate to join the study. "We're almost up to 20 [subjects]," he says, "and I've tried to keep phase one open for just a few more, but each patient requires a huge amount of paperwork. We need to move on to phase-two testing, which will look for statistically significant evidence that it really works. Then there will be more places open, but you'll have to meet very specific criteria to be accepted. So I've stopped answering my phone, because I can't keep saying no to people. It's depressing. I guess doctors learn how to tell people they can't help them. But I'm not a doctor."

He's right about doctors. Jean Decety, a psychologist at the University of Chicago, compared a group of doctors with laypeople, watching a video of patients receiving a painful acupuncture treatment. In the laypeople, parts of the brain associated with pain and with empathy were activated, but in doctors those circuits were suppressed, Decety found. Instead, they showed activity in areas associated with logical thinking. Decety said he wasn't surprised by Davis's experience.

"Doctors see people dying all the time," he said, "and if they couldn't modulate their emotions, they couldn't get through the day." So you may be smart enough to cure cancer, but first ask yourself: are you tough enough?

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