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.)


  1. There's a conventional warning/wisdom about cures in mice/rats not always translating easily or at all to humans so would wonder if will apply here. With continued building on himself and 4 companies doing follow-up on Bradner's work certainly increases possibility it can be development further to actual treatments.

    1. Yeah, I'm all for his work. It's just that too much of this profile is "He Gave Away Millions!", when it should be "Academic publishes tool compound structure somewhat sooner than usual."

  2. Thanks for pluggin' my story plus that of the fantabulous Michael Torrice. I think it'd be great to have more 'reporter boot camps' where folks could learn about the drug discovery process, sort of like a Drew Residential School on Medicinal Chemistry for reporters. (Drew U. alum here!) But the sticky wicket is always who would fund such a thing. I can't imagine reporters would go for something pharma-funded if they were going to cover drug discovery, for conflict-of-interest reasons. The Knight Foundation offers a medical evidence boot camp, but I don't know how much drug discovery really gets covered there. It's more of 'here are the skills you need to determine whether a clinical trial met its endpoints'.

  3. Open source sharing of data, methods, and tool compounds is a good idea and not at all new, even in practice.

    That's central to the whole Molecular Libraries Probe Chemistry Network sponsored by the NIH for the past 5 years (and ending soon). Find a new target, do an uHTS, optimize / analog hits to find a lead, validate mechanism of action, publish results and data for a tool compound, deposit material with the NIH to share with people everywhere.

    It's good to see such efforts getting publicized.

  4. Oh the media... This seems an appropriate thread to post the recent NY Times article about Paul Chirik (Princeton) working on iron catalysis

    To use your phrase, "hagiographic" also seems to apply here. "Dr. Chirik, 39, has learned how to make iron function like platinum, in chemical reactions that are crucial to manufacturing scores of basic materials."

    Hmmm... I dont quite agree.. though it is good to see inorganic chemistry in the media in some context at least.

  5. The compound is not Jay's molecule. Mitsubishi patented very close if not identical compounds way back and even Jay himself acknowledges where he got the idea from.

  6. Anonymous is correct. The molecule came from Mitsubishi, via GSK, via the SGC. There's an unfortunate contrast between how much praise is heaped on Bradner by some lazy commentators and the tiny amount of recognition given to others who were far more influential, but I suppose one narrative fits the "academic drug/tool discovery" agenda very well. One day maybe the whole story will come out.

  7. Honestly it's lazy and insulting for several reasons.
    --a paper = a drug. (Marcia Angell et al)
    --NIH does research, drug companies just make profits. (Donald Light, et al)
    --science should be done purely for the love/joy, not for money (Madeleine Jacobs)
    --single-genius did it all (thx commenters above for pointing out Mistubishi, GSK et al)
    --funding page on Bradner Lab has 11 sources, also a Donate button
    --academics pay themselves on top of salary with a cut of their grants
    --does anyone really think Harvard doesn't maximize their IP?

    It's nice to see positive reviews of science or scientists but unresearched puff pieces like this do more harm than good.