What Happened? Why Hillary Lost..My Take

 By Shlomo Maital

Hillary Clinton has now published her account of why she lost the presidential election: What Happened?   She admits to blame, but also blames many others, including the Russians and Comey.

     She also notes how she was unnerved at a crucial debate, when Trump lurked behind her, scowling. And a headline even praises her for ignoring Trump (see above).

   I disagree. Her is my take on an alternative scenario.

       Hillary:   turning and pointing at Trump.   “Is that the person the American people want to lead them?   Come out here, Mr. Trump, come out into the light where we can see you for what you are – a bully. You bully everyone, you bully women in particular – but Mr. Trump, you can’t bully me. I’m not afraid of you. A man who bullies, who hides in the shadows as you do in your shady business dealings, in your shady bankruptcies, in your hiding your income tax returns…   you are not worthy of the trust of the American people. We don’t like bullies. We don’t like liars. And we don’t like men who threaten women.   We are going to thump Trump on November 8! Thump Trump!”

     Hillary was the first female U.S. Presidential candidate. I recall that Israel had a woman Prime Minister, Golda Meir, who was widely believed to be a lot tougher than her male counterparts. Many criticized Hillary for her emails, her lack of human warmth, etc.   I think she would have won Ohio (and hence the election) if she had shown another quality – toughness. The irony is, Hillary is indeed tough. But the toughness was shown only in private, and rather hidden in public.   Alas!  

 

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How to Help Creative People: Be (Or Support) Claude Shannon’s

 By Shlomo Maital

Claude Shannon

   Claude Elwood Shannon (1916- 2001) was an American mathematician, electrical engineer, and cryptographer. He invented what we today call known as “information theory” – the foundation of software, computers and cell phone technology.

   According to Wikipedia: “Shannon is noted for having founded information theory with a landmark paper, A Mathematical Theory of Communication, that he published in 1948. He is, perhaps, equally well known for founding digital circuit design theory in 1937, when—as a 21-year-old master’s degree student at the Massachusetts Institute of Technology (MIT)—he wrote his thesis demonstrating that electrical applications of Boolean algebra could construct any logical, numerical relationship.” In other words, you can do anything with 0,1.  

   NATURE magazine (July 13 2017, p. 159) has a review of a new book about Shannon, A Mind at Play: How Claude Shannon invented the Information Age. The review is written by Vint Cerf, who designed the architecture of the Internet.

     At the close of his review, Cerf notes:   “What emerges is a portrait of an exceptional free-spirited mind, nurtured by colleagues at MIT and Bell Labs….he was protected from some of the more mundane aspects of work, such as reporting progress, by colleagues and managers. They recognized his unique ability to wrestle insight from complexity, by peeling away details that obscured the kernel of problems and inviting creative solutions”.

     What I learn from this is:   Be like Shannon. Strip away the humdrum things you do, and focus on big problems, on the core of the problem. Peter Drucker taught “Innovation and Abandonment” and he began with ‘abandonment’. That is, what can you get rid of in your life that takes away time and energy from your creative powers? How can you be like Shannon?

     And, next best, if you cannot be like Shannon, can you identify and support other people around you who are like Shannon?   Supporting other creative people may be as important as being creative yourself.

How to Cure Cancer: Zelig Eshhar and the $12 b. Exit

By Shlomo Maital

Prof. Zelig Eschar

  Last year, I blogged about a remarkable breakthrough in research on fighting leukemia and lymphoma.

“Media reports last week [2016] brought exciting news about a new breakthrough in the fight to cure cancer. Cancer patients received genetically modified T-cells that were equipped with synthetic molecules called chimeric antigen receptors, or CARs. Those T-cells were able to target and destroy the tumor cells – specifically the ones that were responsible for the acute lymphoblastic leukemia the patients were suffering from. According to officials at the Fred Hutchinson Cancer Research Center, where the research was carried out, patients in the trial – some of whom were told in 2013 they had barely a few months to live – not only survived, but now, after the therapy, “have no sign of the disease.”   One of the pioneers of this approach is Prof. Zelig Eshhar, of Israel’s Weizmann Institute. According to press accounts:   “Eshhar has been conducting T-cell research for over a decade, and in 2014 was recognized by leading industry publication Human Gene Therapy for his work, along with Dr. Carl June of the University of Pennsylvania for their work in the field.”

Yesterday brought an interesting postscript, with an Israeli perspective.

    Kite Pharma, a US company founded by an Israeli scientist, Dr. Arie Belldegrun, acquired the patent rights to Eschar’s breakthrough, in a very complicated deal. Now, according to the Wall St. Journal, a biotech company called Gilead (“Balm of Gilead”, from the Bible), with $30 b. in annual revenues, has acquired Kite Pharma, for a staggering $12 billion. And that figure is not overpriced.

   One reason for the high price is that recently Novartis received FDA approval for a similar drug, based on genetically engineering T-cells to recognize and kill cancer cells, this one for leukemia.   Kite and Gilead may soon get FDA approval for their drug aimed at non-Hodgkin’s lymphoma.

   Belldegrun is a remarkable individual.   He is a Professor at UCLA, a specialist in urological oncology. And at the same time he is a serial, successful entrepreneur, having done several exits (and earned many hundreds of millions of dollars), and is founder of Kite. He recognized the potential of Eschar’s breakthrough and managed a complex deal in which Kite acquired the rights to the patent. Belldegrun studied at Israel’s Weizmann Institute and Hebrew University Medical School, and moved to the US early in his career. He collaborated closely with Dr. Steven Rosenberg, of the U.S. National Institutes of Health.

     The new approach to fighting cancer – teaching T-cells how to spot cancer cells, which are cleverly disguised, tear off their disguise and kill them – is highly promising. Kudos to Professor Eschar, Dr. Belldegrun and to those who were early investors in Kite – and profited.

 

Crowd-Sourcing Hard Problems, as Games

By Shlomo Maital

   One of the hardest problems in molecular biology is discovering the exact 3-dimensional structure of complex protein molecules.

     Scientists at University of Washington, Center for Game Science, in collaboration with the Department of Biochemistry, found a unique way to tackle the problem. They crowd-sourced it, by creating a kind of social game in which players collaborate to find protein’s 3D structure – how the protein molecule ‘folds’. The game is called FoldIt. A recent BBC program decribed it.

    Foldit attempts to apply the human brain’s three-dimensional pattern matching and    spatial reasoning abilities to help solve the problem of protein structure prediction. Current puzzles are based on well-understood proteins. By analyzing how humans intuitively approach these puzzles, researchers hope to improve the algorithms used by protein-folding software. Foldit includes a series of tutorials where users manipulate simple protein-like structures and a periodically updated set of puzzles based on real proteins. It shows a graphical representation of each protein which users can manipulate using a set of tools.

      But did anything useful emerge? Indeed it did.

* A 2010 paper in science journal Nature credited Foldit’s 57,000 players with providing useful results that matched or outperformed algorithmically computed solutions.

* In 2011, Foldit players helped decipher the crystal structure of the Mason-Pfizer monkey virus (M-PMV) retroviral protease, a monkey virus which causes human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (HIV/AIDS), a scientific problem that had been unsolved for 15 years. While the puzzle was available for three weeks, players produced an accurate 3D model of the enzyme in only ten days.

* In January 2012, Scientific American reported that Foldit gamers achieved the first crowdsourced redesign of a protein, an enzyme.

    We know young people are bored in school. What if we could teach them math and science through a gaming approach? Challenge them with hard problems, let them work in teams (get those smartphones out of locked cupboards and put them to work) and ignite their creative energy.

   Surely, somewhere, progressive schools are doing this?

 

Why Ideas Resemble Pearls

By Shlomo Maital

       Pearls are one of nature’s many wonders. It occurred to me that ideas are born in ways similar to pearls. How come?

       Pearls form when a microscopic ‘intruder’ or parasite invades an oyster.   (Rarely, a grain of sand…mainly parasites). This irritates the oyster. In defense, it starts to coat the intruder with a form of calcium carbonate. Layer upon layer of calcium carbonate coat the intruder, until it is harmless. Then, perhaps, a pearl fisher is lucky enough to find the resulting pearl. Millions of years of evolution have given oysters a vital tool for survival.

       The process in oysters is not unlike the human immune response – a germ invades our body, and our antibodies (usually T cells) grab the invading antigen and capture and neutralize it.

       So why are ideas like pearls?   Ideas can form when creative people are irritated by something we see or hear. For instance — on the street, I see an elderly person struggling with a cell phone, trying to see and punch numbers on a cell phone meant for fingers fifty years younger.   I am irritated. Why should this happen? Why are the elderly humiliated and ignored?  

       That irritation is like the invader of an oyster. Immediately, the creative brain goes to work, often subconsciously, working on ‘neutralizing’ the irritation by finding a solution… coating it with many ideas that solve the problem. And if you listen carefully, some of those ideas pop into your conscious mind, like lovely pearls waiting to bring happiness to the world…but only if you crack open that oyster, find the ‘pearl’ and ACTIVATE – do something with it.

     This is how memory sticks were invented. The inventor Dov Moran forgot to plug in his laptop and lost his presentation, in 1986. He swore at that moment, through irritation, that never again would this happen. The result: his startup M Systems invented the memory stick. The memory stick was the pearl that Moran formed, around that initial sharp irritation.

     The lesson here? Be passionate. Be empathetic. Care about what goes on around you, and care about people who struggle, suffer, are in pain, or who simply have unmet needs. Feel the injustice! Then let your creative brain eliminate the irritation by finding a solution or solutions.

       Natural pearls are rare and expensive, and adorn women with means. But natural ideas cost nothing and change the world. All that is needed is that initial tiny irritation – a feeling caring person whose irritation at injustice and pain goes away only when a creative solution emerges from it.

 

Seek Creativity? Talk to Yourself!

By Shlomo Maital

  My wife Sharona is a school psychologist, and for many years has spoken to me about the work of a pioneer Russian psychologist, Lev Vygotsky, who studied children and gave the world breakthrough insights. in the 1920s.  One of those insights: “when children learn to talk to others, they also learn how to talk to themselves, first out loud, and then in their heads”. And that “inner speech”, it turns out, is crucial.  

     In the latest Scientific American, psychologist Charles Fernyhough discusses his new book The Voice Within – about our inner speech.

     It is a worn cliché that people who talk to themselves out loud are kind of nutty. But of course, we all talk to ourselves silently, in our heads. I talk to myself for motivation, when I am working out or tackling something rather hard or running up a hill and tiring. Fernyhough notes that inner speech has a role in emotional expression (I sometimes say hard things to those around me, but – only in my head, I have learned not to say them out loud), and at times, I talk to myself to try to understand myself. What do I really think about that?

     Fernyhough notes that inner speech has a role in imagination, in creating alternate realities. I think this is very important.   Part of creativity (creating things that are both novel and useful) is to understand what is truly useful. To do that, you need to have empathy – that is, you need to understand not just how you yourself feel but how others feel.   Inner speech can help. Your inner speech expresses what other people might think and feel about your creative idea. If your inner speech is truly honest, and not just empty self-motivation, it can be helpful in validating your ideas.  

     Let’s say I have an idea for a new-fangled potato peeler, with a squishy handle. I make a prototype. I hold it in my hand. And my inner speech says how another person would feel in holding and using the device.

   I think there is another use for inner speech. Suppose you have to make a tough decision – whether to quit your job and accept a risky position with a startup.   Engage yourself in debate. Take both sides.   Argue with yourself. Verbalize all sides, all aspects. Then, stop. Do something else. Go for a walk or a run.   Your subconscious brain will grab that inner speech, and process it, thoroughly, and send you (very quietly) an answer — so you’d better be listening. When you hear that answer, verbalized, and motivated, you can probably rest assured that this is what you should do.

       So – try doing more inner speech. Talk to yourself. Get better at it. Sometimes, it might help to say the words out loud. Sometimes, you just have to think them.   Putting thoughts into words is an important way creative people have in taking the initial steps to implementing their ideas.

 

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.

How to Live to 114

By Shlomo Maital

Yisrael Kristal

   The world’s oldest man, Yisrael Kristal, passed away quietly in Haifa on Friday August 12 and was buried the same day.   He was officially recognized by the Guiness Book of Records.   It is said that only the righteous die on the eve of the Sabbath.

   Just think of what this man lived through. He was born in Zarnow, Poland, on Sept. 15, 1903, to a religious family, 3 months before the Wright Brothers made the first manned flight. When he was 10 his father fought in World War I and was taken prisoner. His father died in 1919.     Kristal learned how to make candy and opened a factory in Lodz. He married his wife Feige, and at the onset of WWII they had two sons, aged 8 and 10.   Both sons died in the starvation conditions prevailing in the Lodz Jewish ghetto.  

   During the initial years of Nazi occupation, Yisrael survived because of his candy-making skills. The Nazis had him make confections for their parties. But in May 1944 he and his wife Feige were sent to Auswicz. When the camp was evacuated, they did the Death March. Kristal survived, in the end weighing only 37 kgs. (80 pounds). Feige perished.   At the end of the war, Kristal returned to Lodz and re-opened his candy factory.   There, he married Bat Sheva, who also had lost all her family to the Nazis. In 1950 they emigrated to Israel, and had children.  

       At the age of 113, Yisrael had his bar mitzvah – delayed by 100 years owing to the Holocaust. His great-grandchildren, grandchildren and children celebrated with him.

     He was lucid to the end. He remained in his own home almost to the end – his son, a doctor, cared for him, and had him moved to a hospital on Wednesday Aug. 10; he died peacefully two days later.

       The secret of his longevity?   Optimism. He loved his country, and was a perpetual optimist. I think he found immense satisfaction in building a new family, with many great-grandchildren, in a new country, and outliving his persecutors.  

       Optimism and hope for the future are wonder drugs. We should use them more widely, even if we are not 114 years old.

Fixing Bad Genes: A First!

By Shlomo Maital

Shoukhrat Mitalipov  

   Virtually at the same time — President Trump proposes legislation to limit immigration to the U.S. and an immigrant from Kazakhstan named Shoukhrat Mitalipov manages, for the first time, to ‘edit’ mutated genes in embryos and ‘cure’ genetic disease, enabling the babies to be born healthy.

     This is hugely significant. Parents who undergo genetic testing, and who test their unborn babies, are at times tragically told: Your unborn infant carries a ‘bad’ gene that will make him sick or even die.

       The parents ask: What can we do?

       The tragic answer, until now — Nothing. Abort or —     accept its fate.

         There have been 3 previous published instances of gene editing, all in China.   According to MIT Technology Review:   “Now Mitalipov is believed to have broken new ground both in the number of embryos experimented upon and by demonstrating that it is possible to safely and efficiently correct defective genes that cause inherited diseases. Although none of the embryos were allowed to develop for more than a few days—and there was never any intention of implanting them into a womb—the experiments are a milestone on what may prove to be an inevitable journey toward the birth of the first genetically modified humans.”

   How did he do it?

   Mitalipov and his team used CRISPR Clustered regularly interspaced short palindromic repeats. CRISPR is now the dominant technology for gene editing. Try as I might, I do not know enough biology to explain how it works. The initial work was done in Japan, at Osaka University.

     CRISPR often makes mistakes – disastrous if you are trying to heal a bad gene. Mitalipov figured out how to avoid those mistakes.

   Who is he?

   “Born in Kazakhstan when it was part of the former Soviet Union, Mitalipov has for years pushed scientific boundaries. In 2007, he unveiled the world’s first cloned monkeys. Then, in 2013, he created human embryos through cloning, as a way of creating patient-specific stem cells.”

       Is it coincidence that Mitalipov is an immigrant? I don’t think so. By definition an outsider,   such ‘outsiders’ try daring things that those comfortably within the establishment might not.

     Is there any reason to worry?

   Yes.  We can genetically modify embryos. We can do this to cure gene defects – or to modify embryos to make taller kids (NBA), smarter kids (Einsteins), or handsomer kids, or blonde kids… etc.

       “Some critics say germline experiments could open the floodgates to a brave new world of “designer babies” engineered with genetic enhancements—a prospect bitterly opposed by a range of religious organizations, civil society groups, and biotech companies.  The U.S. intelligence community last year called CRISPR a potential “weapon of mass destruction.”

 

 

The Death of Imagination

By Shlomo Maital

   Tuesday’s New York Times has an article, “How to make a movie out of anything”, by Alex French. In it he describes how Hollywood producers are desperately searching for IP, slang for intellectual property, as the basis for movie scripts. Translation: Find something people recognize easily, and build a plot around it.

   Examples: the Lego movie; the recent Emoji movie; the Angry Birds movie; and soon, yes, the Fruit Ninja movie.

     So what’s wrong with that?

     I grew up in the 40s and 50s, in the era of radio. I listened to Boston Blackie and the Cisco Kid. I heard horses hooves, a pistol firing…and I had to imagine the horse, the revolver… everything.

       Today? In the era of TV, MTV and virtual reality and smartphones – all the images are there, given to us…no need to imagine. A Lego movie? Lego is building blocks. How can you make a blockbuster Lego movie? Turns out that you can – if you start with something people are familiar with, they do not need to use their imaginations.   But if you start with a conventional movie plot, a story, however strong, people need to imagine – and it looks like our young people no longer can. We need to have the images stored in our brains already, because…we’ve lost the ability to create them ourselves.  

   This sounds like a cranky old curmudgeon yearning for the good old days. Perhaps.   But if this new Hollywood trend portends the death of imagination – then we’re in real trouble. Worse yet, nobody seems to care much.

Blog entries written by Prof. Shlomo Maital

Shlomo Maital
September 2017
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