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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.

Cultivate More Stress! Really!

By Shlomo Maital

Tiger Woods is one of the world’s greatest golfers ever, in a league with Palmer, Niklaus, Snead, and Bobby Jones.  He has had personal problems, a messy divorce, back injuries, surgery, and lately hasn’t made the first cut in tournaments.

     Woods was stopped by police, in his car, near his home in Florida, and failed a breathalyzer test. But he had no alcohol in his blood. He had simply taken tranquilizers and fallen asleep; he took enough of them, so that he could not walk a straight line.

     Let’s get this straight. No game has more stress than golf. That final putt? Make it and you win a major. Miss it and you finish second or third – not good. Stress? You bet. Yet doctors have doped up Tiger with Xanax (a blockbuster tranquilizer, making billions for Pfizer), Vicoden, Vioxx and who knows what else. Was he taking Xanax while playing? If so – no wonder he missed the cut.

       Be clear – Xanax is a wonder drug for those who suffer extreme anxiety attacks. Yet it is according to US Food and Drug the most abused tranquilizer, prescribed for millions who do not need it. Why? Because we’ve been taught by Big Pharma and others, that stress is harmful, terrible, to be avoided at all costs, by popping a pill. So pop away…. and help that bottom line of Pfizer.

         I argue here that we need more stress, not less. What is stress? Stress is “a state of mental or emotional strain or tension resulting from adverse or very demanding circumstances.”   Simply put — We have an unsolved problem, and it bothers us.   Let’s redefine stress.   “…a challenge, that when we solve it (not if), boosts our self-esteem, self-efficacy and our sense of wellbeing”.   Need a pill for that? No. You need to take on the challenge and crack it. Creativity is widening the range of choices. To meet unsolved problems, we can come up a large range of possible solutions. Zoom in, pick one – and go for it. Sometimes you will fail.   That’s part of life. Sometimes you’ll succeed. But if you Xanax the stress, you’ll never get even the chance to succeed.   When you tackle a stressful state, you change your mental outlook from anxiety to action….it’s that simple.

         And – keep in practice. Purposely seek out hard things to do every day, and do them, and feel good about it.   This is super-important for us seniors. It is so easy to pamper yourself, when you’re over 65, just because you have grey hair. Why? Take on challenges. Your body may not be as strong, but your mind sure is.

         Do not be manipulated by Big Pharma.   Welcome stress. Cultivate it. Tackle those big challenges – and crack them.   You can do it.  Popping a Xanax smothers the stress, temporarily, but doesn’t deal with it. It’s not a solution.  

Pop a Pill? No! There’s a Better Way

By Shlomo Maital

Aziz Kaddan

Aziz Kaddan, Amir Khalaily, Hilal Diab, Anas Abu-Mukh

   Arab culture is highly entrepreneurial.   Given the right opportunities, Arab entrepreneurs could transform the Arab world, shifting Western attention from ISIS and its vicious violence to IS (Innovation Startups).  Here is an example (thanks to Sharona, my wife, who drew my attention to this story).

     ADHD attention deficit hyperactivity disorder  is widely treated with a drug, Ritalin.  Novartis sells $350 m. worth of methylphenidate (Ritalin) each quarter.  When kids have problems in school, it’s super easy for teachers to demand that they pop a pill – even if the problems could be addressed differently, with a little effort.  In general, our pop-a-pill society plays into the hands of Big Pharma, and sometimes does immense harm to us all.  Ritalin is now used widely as a recreational drug, too.   For Big Pharma, it’s all just money.

      NASA developed a computer-based technique to improve attention, focus and learning.  Now, Aziz Kaddan, age 22, an Israeli Arab,  and three friends have launched a startup, Myndlift, that uses biofeedback to deal with ADHD.  It’s an app-based wearable solution, together with mobile games that work only through attention, and boost attention levels with only 10 minutes of play time a day.  Kaddan is the son of a neurologist, and got a computer science degree at the age of 19. 

       Friends urged Kaddan to up the price of his app (it’s only $15 for the premium version), but he and the founders believe that to keep this solution accessible, it has to be quite cheap.  (Big Pharma – don’t you just love it?). 

      Over the years, I’ve taught many students with ADHD.  Most of them avoided Ritalin, and instead developed their own personal unique ways to focus and deal with their challenges.  Sometimes, the ADHD was even a blessing, because it appears that those with ADHD happen to be very creative. 

      Next time you have a problem, and someone tells you to pop a pill,  think about it for a while.  Sometimes you really do need that pill.  Sometimes, you can manage better without it.

 Thanks to  Aziz and his friends for showing us another way, other than pill popping.  I hope their story will inspire other Israeli Arab entrepreneurs.


Vaccines: Time for Legislation

By Shlomo Maital


  New York Times report Elisabeth Rosenthal reveals to us another Big Pharma ripoff – this time related to vaccines.   When in the world will the U.S. Congress act to end this travesty?

   According to Rosenthal, Big Pharma uses the ‘new improved yogurt’ trick to fatten profits and hurt the middle class and the poor.  If you sell price-regulated yogurt,  change the package, add something (fermented kiwi juice) – and claim it is a new product, hence not subject to the old price controls.

   In vaccines Rosenthal writes:

     “Old vaccines have been reformulated with higher costs. New ones have entered the market at once-unthinkable prices. Together, since 1986, they have pushed up the average cost to fully vaccinate a child with private insurance to the age of 18 to $2,192 from $100, according to data from the Centers for Disease Control and Prevention. Even with deep discounts, the costs for the federal government, which buys half of all vaccines for the nation’s children, have increased 15-fold during that period. The most expensive shot for young children in Dr. Irvin’s refrigerator is Prevnar 13, which prevents diseases caused by pneumococcal bacteria, from ear infections to pneumonia. Like many vaccines, Prevnar requires multiple jabs. Each shot is priced at $136, and every child in the United States is required to get four doses before entering school. Pfizer, the sole manufacturer, had revenues of nearly $4 billion from its Prevnar vaccine line last year, about double what it made from high-profile drugs like Lipitor and Viagra, which now face generic competitors.”

Let’s see that again. A price rise from $100 to $2,192???   And remember vaccination is not optional; it is essential for the lifetime health and wellbeing of every child.

  Half of all vaccines are bought by the U.S. federal government. Their costs have risen 15-fold!   Why is it that when we ordinary folks get ripped off, we scream – but when Big Pharma rips off the government, there is silence?? At a time when deep budget cuts are hurting everyone?  

   When one company, Pfizer, makes $4 billion from ONE vaccine, Prevnar, double what it makes from a high-profile blockbuster drug, something is radically wrong. Wake up America!

Blog entries written by Prof. Shlomo Maital

Shlomo Maital