Fighting Cancer: Open Source Drug Discovery

By Shlomo Maital


 Here is how drug discovery works. Big Pharma companies invest big bucks, fail with many promising drugs, find one that works – and then charge fortunes for it to recoup their original investment.  This model, quintessential capitalism, is not working too well, because many illnesses are under-researched, when the nascent business model does not indicate big profits. Alzheimer’s is an example. (Biogen’s stock, however, shot up when it announced a promising Alzheimer’s Drug… an exception to the rule).

     Along comes young Jay Bradner, with a new idea, described in his TED talk and in the TED Radio hour on WBUR.

       “In 2010, Bradner secured his reputation as an innovator when, rather than guarding his discovery of a breakthrough small molecule, he began sharing the compound with other scientists in the field. The molecule, JQ1, inhibited a family of proteins known as bromodomians, and showed promise for blocking the growth of certain cancer cells. Since 2010, the Bradner lab has shared 15 different compounds with more than 450 laboratories worldwide.   This month, Bradner unveiled his latest breakthrough: a new chemical technology platform to destroy proteins in cancer cells. The finding, published online in Science Express, could pave the way for new inhibitors for previously “undruggable” targets.”

    Let’s get this straight. Bradner makes a discovery that could make him and his lab (Dana Farber) wealthy. Instead of patenting the molecule – he publishes his results and offers samples of it to anyone who asks!  

     Could this disrupt the Big Pharma Big Greed industry as a whole? And wait – didn’t his employer the wonderful Dana Farber Cancer Research institute in Boston, hassle Dr. Bradner?

     To Dana-Farber’s credit, there was little resistance. The profound burden of cancer and the complexity of cancer genetics both call not only for new therapeutic technologies but also new strategies for therapeutic discovery.

         The advantage of Bradner’s approach? Many many more researchers will work on these molecules, test them, and perhaps modify and improve them. As a result, drugs that work on a variety of forms of cancer may reach ill people much sooner. Lives will be saved.

There are two key points here.

       One is – Innovation is not just about WHAT you discover, it is about how you go about making breakthrough discoveries. Discover, test and patent?   How about, discover, and give it away to all who ask!   I sometimes teach my students that they should put their ‘baby’ (their wonderful idea) up for adoption and give it away.   Give it to someone who has the means and ability to implement it, and even make them believe it was their idea. If you really want to change the world, sometimes, that is the only way.

   Needless to say — I have a very hard time selling this idea.   Investors want ‘intellectual property’ – even though the knowledge and skills that give birth to them often come from universities funded by public money. And some universities want to patent anything that breathes, if it breathes on their physical grounds.

   How well has this open-source model worked? (Note: For some types of software, it has worked exceedingly well. Ever heard of Linux?):

    Second: Open Source speeds research and gets faster results.  Here is what Bradner reports:    “It’s funny – there is no obligation for recipient laboratories to report research findings, but almost everyone does. Labs may reach out to request more material, perhaps for in vivo studies, but most write or call just to share their incredible findings. We’ve also experienced how powerful chemical probes are in target validation. In response to a questionnaire we sent laboratories that received JQ1, 50% of investigators responded that their work with the compound led to a disease-specific clinical opportunity.   Finally, we learned that compounds are powerful vehicles of experimental reproducibility, a major issue in science today. In two research areas, two or more groups have simultaneously published mutually supportive stories on BET bromodomain biology using JQ1.   Beyond these lessons, the open-source strategy has been a wonderful introduction to research fields that I might not have otherwise had an opportunity to access. We have fantastic collaborators in cardiovascular disease, tissue remodeling and fibrosis, and reproductive biology. Though my group focuses on chromatin and chemical biology largely in the area of cancer, these collaborations have broadened our research horizons significantly.”

    And just to show that ‘open source’ is truly a part of Bradner’s DNA, the name of the key molecule JQ1 comes from the researcher in his lab who first discovered it, a scientist named Jun Qi.   Not JB1.  JQ1.  Well done, Dr. Bradner.

     If only more labs, and more inventors, could learn the key principle, that creativity is like love – the more of it you give (away), the more of it you (and society) get back.