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The nanoparticles carry fluorescent and magnetic tags to make the tumors visible. Eventually, they may also carry drugs to kill any cancer cells left over after surgery. One obstacle is that other enzymes in a normal liver can also cut off the “backing paper” as currently designed, so that the liver picks up a lot of the nanoparticles. That doesn't matter for surgery, but it could be a problem for delivering cell-killing drugs.
In transgenic mice with an especially aggressive form of breast cancer, surgical removal of the tumor offers only a 10 percent chance of tumor-free survival. But when Nguyen and Tsien made them glow, tumors were visually distinguishable from healthy tissue; tumor removal was more complete, and tumor-free survival quadrupled to 40 percent.
“[Tsien] can visualize, almost anthropomorphize, molecules in a very astute way, so that things work,” explains Nguyen. “He really has a sense of how these molecules interact.”
Their results, while not yet published, appear to bear out Nguyen's praise. In addition to helping the mice live longer, they've tested the technique on biopsied human breast cancer tissue (results they plan to publish with the mouse studies); the cancer cells take up the marker. But, at least for now, mice are the only animals to benefit on the operating table. (As a side project, Tsien and Nguyen are working on a way to make nerves visible during surgery to help surgeons avoid damaging them.)
Between the lab and human trials, Tsien says, “there's something called the valley of death, the gap between promising results obtainable with research funding versus the much more expensive studies necessary to convince companies to invest. Right now I'm looking at that valley of death, which is particularly wide during economic gloom.” He expects that clinical trials to test the safety and effectiveness of the technique in humans will cost millions of dollars.
But the potential payoff is enough to motivate this leap into new territory. “Some of the biggest touted therapies cost hundreds of thousands of dollars per patient treated, and they buy you a few extra months and then you die anyway,” he says. If, for even a few patients who need surgery, he can help surgeons cut out all the cancer, he could buy those patients extra years.
That kind of motivation is what Tsien thinks should drive scientific inquiry. At Janelia Farm, fresh from notice of his Nobel, Tsien admonished the students that if they wanted a successful career in science, they shouldn't be “unduly motivated or impressed” by prizes.
What they should do, he said, is explore research questions that give some form of day-to-day pleasure. They'll need that interest to sustain them through the periods between big discoveries or the times when things just aren't working, when they find themselves staring at their own valley of death.
He acknowledged, however, that are there are some perks to a Nobel win. “Writing for samples is easier now,” he smiled. “People who used to ignore my e-mails are more responsive.”