Monday, October 29, 2012

"Academic publishes anti-cancer tool compound, details at 11"

Just got my new copy of The Atlantic Weekly, with the "Brave Thinkers" section. In it, there's an interesting and slightly hagiographic short profile of Professor Jay Bradner, a physician and chemical biologist (emphasis mine):
Two years ago, after Jay Bradner made a remarkable breakthrough—the discovery of a molecule that, in mice, appeared to trick certain cancer cells into becoming normal cells—he did something unusual. Instead of huddling with lawyers to file for a patent on the molecule, Bradner simply gave his work away. Hoping to get the discovery into the hands of any scientist who could advance it, he published the structure of the compound (called JQ1) and mailed samples to labs around the world. The move, he says, felt like “the more efficient way to do science—and maybe the more honorable way.” 
The open-source approach Bradner adopted is revolutionary in a culture where discoveries are kept secret, often until they can be tested, manufactured, and sold as treatments—a cruelly long process in the face of the cancers he studies. 
The monopoly on developing the molecule that Bradner walked away from would likely have been worth a fortune (last year, the median value for U.S.-based biotech companies was $370 million). Now four companies are building on his discovery—which delights Bradner, who this year released four new molecules. “For years, drug discovery has been a dark art performed behind closed doors with the shades pulled,” he says. “I would be greatly satisfied if the example of this research contributed to a change in the culture of drug discovery.”
Walked away! A fortune!

I was even more amused to read a somewhat different description of the compound from C&EN's Carmen Drahl in 2010: "We consider JQ1 a tool compound,” Knapp says. “It allows us to study how these readers participate in the development of disease.” Dana-Farber has filed for patents on (+)-JQ1 derivatives that might inspire drugs to treat diseases." Recent readers of C&EN will remember that JQ1 has other bioactivity as well: "In a paper published last month, the scientists showed that JQ1 causes reversible infertility in male mice (Cell, DOI: 10.1016/j.cell.2012.06.045). Now Bradner and Matzuk plan to use JQ1 as a lead compound to produce a second generation of compounds that are specific to BRDT."

I believe (and hope!) that most of the tone of this profile comes from Dan Morrell, the author of the piece, who may not be familiar with the unlikely odds and various hurdles (oral bioavailability issues, as noted in Prof. Bradner's TED talk on JQ1) that any one particular compound faces on its way to becoming a drug.

Prof. Bradner should be commended for his science and his willingness to rapidly publish his work*, but he need not be praised for walking away from a pile o' pharma cash. It may not have been there in the first place.

*As well as providing samples of JQ1! For one reason or another, this long-time aspect of biology (the mailing of plasmids and the like) has not penetrated broadly into chemistry. (Of course, it probably has something to do with our culture of I-can-make-it-myself.)

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