President Barack Obama

IBM’s Watson to Guide Cancer Therapies at 14 Centers

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‘Humans alone can’t do it,’ oncologist says.

Fourteen U.S. and Canadian cancer institutes will use International Business Machines Corp’s Watson computer system to choose therapies based on a tumor’s genetic fingerprints, the company said on Tuesday, the latest step toward bringing personalized cancer treatments to more patients.

Oncology is the first specialty where matching therapy to DNA has improved outcomes for some patients, inspiring the “precision medicine initiative” President Barack Obama announced in January.

But it can take weeks to identify drugs targeting cancer-causing mutations. Watson can do it in minutes and has in its database the findings of scientific papers and clinical trials on particular cancers and potential therapies.

Faced with such a data deluge, “the solution is going to be Watson or something like it,” said oncologist Norman Sharpless of the University of North Carolina Lineberger Cancer Center. “Humans alone can’t do it.”

It is unclear how many patients will be helped by such a “big data” approach, however. For one thing, in many common cancers old-line chemotherapy and radiation will remain the standard of care and genomic analysis may not make a difference.

Cloud-based Watson will be used at the centers – including Cleveland Clinic, Fred & Pamela Buffett Cancer Center in Omaha and Yale Cancer Center – by late 2015, said Steve Harvey, vice president of IBM Watson Health. The centers pay a subscription fee, which IBM did not disclose.

Oncologists will upload the DNA fingerprint of a patient’s tumor, which indicates which genes are mutated and possibly driving the malignancy. Watson, recognized broadly for beating two champions of the game show Jeopardy! in 2011, will sift through thousands of mutations and try to identify which is driving the tumor, and therefore what a drug must target.

Distinguishing driver mutations from others is a huge challenge. IBM spent more than a year developing a scoring system so Watson can do that, since targeting non-driver mutations would not help.

“Watson will look for actionable targets,” Harvey said, matching them to approved and experimental cancer drugs and even non-cancer drugs (if Watson decides the latter interfere with a biological pathway driving a malignancy).

But Watson has trouble identifying actionable targets in cancers with many mutations. Although genetic profiling is standard in melanoma and some lung cancers, where drugs such as Zelboraf (vemurafenib) from the Genentech unit of Roche Holding AG target the driver mutation, in most common tumors traditional chemotherapy and radiation remain the standard of care.

“When institutions do genetic sequencing, only about half the cases come back with something actionable,” Harvey said, often because it is impossible to identify the driver mutation or no targeted therapy exists.

‘Robot Mouse’ Marks New Step Forward in Neuroscience

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The mouse walked, the mouse stopped; the mouse ignored a bowl of food, then scampered back and gobbled it up, and it was all controlled by neuroscientists, researchers reported on Thursday.

The study, describing a way to manipulate a lab animal’s brain circuitry accurately enough to turn behaviors both on and off, is the first to be published under President Barack Obama’s 2013 BRAIN Initiative, which aims to advance neuroscience and develop therapies for brain disorders.

The point of the remote-control mouse is not to create an army of robo-rodents. Instead, neuroscientists hope to perfect a technique for identifying brain wiring underlying any behavior, and control that behavior by activating and deactivating neurons.

If scientists are able do that for the circuitry involved in psychiatric or neurological disorders, it may lead to therapies. That approach reflects a shift away from linking such illnesses to “chemical imbalances” in the brain, instead tracing them to miswiring and misfiring in neuronal circuits.

“This tool sharpens the cutting edge of research aimed at improving our understanding of brain circuit disorders, such as schizophrenia and addictive behaviors,” said Dr. Francis Collins, director of the National Institutes of Health, which funded the $1 million study.

The technique used to control neurons is called DREADDs (designer receptors exclusively activated by designer drugs).

Brain neurons are genetically engineered to produce a custom-made — “designer” — receptor. When the receptor gathers in a manmade molecule that fits like a key in a lock, the neuron is activated.

Because the receptor does not respond to other molecules, including natural ones in the brain, the only way to activate the neurons is via the manmade one. DREADDs allow scientists to manipulate neurons without implanting anything in the brain.

DREADDs, invented about a decade ago, had been used to turn neurons on or off, but not both. DREADDs 2.0 are the first to do that, scientists led by Bryan Roth of the University of North Carolina reported April 30 in the journal Neuron.

Targeting hunger-promoting neurons, the scientists made mice ignore food bowls or dive into them. Targeting movement neurons, they made mice scamper or stop.

In a competing remote-control technique called optogenetics, engineered neurons are activated upon receiving a pulse of light. That turns them on and off more quickly than with DREADDs, but the hardware required for delivering light to a spot in the brain is invasive and cumbersome.