New Thinking on Alzheimer’s: Time for a Paradigm Shift?

By Shlomo Maital

Scientific breakthroughs come from iconoclastic researchers who are not afraid to smash consensus paradigms. Take, for instance, Prof. Michal Schwarz, of Israel’s Weizmann Institute. Here is what she told this week’s Haaretz (Hebrew) reporter:

           The puzzle I pieced together is correct, and now I see the whole picture – how my research approach,  for years against the consensus, has become one of the central focal points for research on all degenerative (neural) diseases.

     The paradigm shift Schwarz has helped bring about is simple.   Many researchers follow the “I dropped a coin” model – they look for it under the corner streetlight, instead of in dark corners, where it fell, because…. “that’s where the light is”.   Alzheimer’s? Gooey proteins gumming up the brain and causing death?   Look for cures that eliminate or prevent the protein directly, in the brain.  Under the light.

       But Schwarz?     Let’s help the body’s own anti-immune system, outside the brain, fight those plaque accumulations that damage the brain. Last year the Daily Telegraph quoted Dr. Doug Brown, a leading Alzheimer’s researcher: “Repurposing drugs that already work for other conditions could provide us with a shortcut to new dementia treatments, and is a key aspect of our Drug Discovery programme.”  

         Here ‘s how the Daily Telegraph described Schwarz’s paradigm shift, in 2016:   “The drugs, known as PD-1 blockers, effectively prevent the immune system from switching off, allowing a continuous cascade of soldier cells to fight disease and clear out damage in the body. In the case of Alzheimer’s disease sticky amyloid plaques build up which stop brain cells communicating with each other. But when mice, engineered to have Alzheimer’s symptoms, were given injections of the drug the amount of amyloid in their brains halved, and the animals were able to complete a maze task in the same time as control mice.  Last year the first PD-1 blocker drug Keytruda was approved for use on the NHS by the National Institute for Health and Care Excellence so it is already known to be a safe treatment.

        “Lead author Prof Michal Schwartz of the Weizmann Institute of Science, Rehovot, Israel, said that in Alzheimer’s a weakened immune system could be preventing the body from repairing itself.    “We are extremely excited about our new study, we believe it is a game changer both conceptually and therapeutically,” she said.

      Her research was published in the leading journal Nature Medicine.

       Prof. Schwarz added: (in Hebrew):   “In contrast to veteran old-time researchers, students have no history of believing dogma (existing paradigms)…they are fresh ears and eyes, without preconceptions. They were especially excited, with me, at our results, and joined my research and contributed to moving it forward, and some of them are continuing in my wake.”

         As a (very) senior citizen, I have deep interest in breakthrough research on Alzheimer’s – half of those over 85 have it, at least early versions.   Congratulations to Prof. Schwarz for becoming a woman scientist and for leading a paradigm shift that may help millions – including those in countries that despise Israel.

 

The Age of Wonkery

By Shlomo Maital

   In his New York Times Op-Ed piece, April 11, David Brooks supplies a crucial insight.

     Once the thinkers of the world were intellectual foxes. In Isaiah Berlin’s metaphor, they had many many ideas and challenged all of them.

     Today? We have wonks.   They are hedgehogs. They have one BIG idea. And they sell it ferociously, regardless of the facts.  In truth — they have given up thinking. 

     As Goethe observed, thinking is better than knowing (i.e. foxes are better than hedgehogs),   but …looking is best of all. And wonks do not look (at the facts).   Nor think about their Pablum ideologies.

       So – we are doomed to live in the Age of Wonkery. Not too good for humanity.

       Here is how Brooks frames it:

“People today seem less likely to give themselves intellectual labels or join self-conscious philosophical movements. Young people today seem more likely to have their worldviews shaped by trips they have taken, or causes they have been involved in, or the racial or ethnic or gender identity group they identify with. That’s changed the nature of the American intellectual scene, the way people approach the world and the lives they live.   In his book, “The Ideas Industry,” Daniel W. Drezner says we’ve shifted from a landscape dominated by public intellectuals to a world dominated by thought leaders. A public intellectual is someone like Isaiah Berlin, who is trained to comment on a wide array of public concerns from a specific moral stance. A thought leader champions one big idea to improve the world — think Al Gore’s work on global warming.”

Brooks does not say this but —   not only is President Trump a super-wonk but – he has peppered his so-called administration with similar super-wonks, who are not troubled by facts.   And in upcoming elections in France, Germany and elsewhere, we see rising political parties featuring wonkery at its extreme (e.g. get rid of foreigners, anyone not like us, that will solve our problems).

     What does this mean for thinking people? Continue to fight. Challenge unsupported ideas. Build on facts. Dig up the facts. Think through issues. And above all embrace complexity.   Wonks simplify…violating Einstein’s rule, simplify as much as possible – but not more so.   Life is complex. Truth is complex. It cannot be reduced to a single variable, a single formula.    

   Wonks succeed because people are confused by complexity and want simple formulae.   Don’t give in.   Embrace complexity as a way of embracing truth – and fight back.

Creative Genius at 94: Here’s How!

By Shlomo Maital

John Goodenough and his team at University of Texas (Austin) “have just set the tech industry abuzz with his blazing creativity”, writes Pagan Kennedy, in the New York Times.   “He and his team filed a patent application on a new kind of battery that, if it works, as promised, would be so cheap, lightweight and safe that it would revolutionize electric cars and kill off petroleum-fueled vehicles.”

   This is not Goodenough’s first invention. At age 57 he co-invented the lithium-ion battery that shrank power into a tiny package; such batteries now exist in nearly all devices at home and at work.

     OK – another genius. Nice. But what is unusual about Goodenough???

     His age.

       He is 94 years old.

       I often speak to groups of senior citizens, and tell them to restart their creative brains… reject the idea that you have no ideas under gray hair. It’s false!!   I know a Technion colleague who invented an amazing cure for cancer after age 70.  

       Here is what Goodenough says:   He started in physics, meandered through different fields, picking up clues as he went along. He hopped sideways into chemistry and materials science, keeping his eyes on social nad political trends. “You have to draw on a fair amount of experience in order to be able to put ideas together”, he notes.

     PUT IDEAS TOGETHER!   That is creativity. And who can do it better than 94 year olds, who have seen and learned so much about life?

       Thanks John! I’m 74. So maybe in two decades I will still have ideas….that create value.

       Remember the name: Goodenough. What is,   was not good enough for Goodenough. Even at 94.

 

Thinking in the Bubble:   How to Detect Land Mines

By Shlomo Maital

Writing in the Hebrew daily Haaretz, today, Ruth Schuster reports on a clever creative invention by Hebrew University scientists.

   The problem: undetected land mines.

   “Land mines are the scourge of the survivor. They lurk in the soil for years and even generations after the fighting ends. Up to 20,000 people a year are wounded or killed after stumbling on hidden mines, and there has been no safe way for man or beast to detect them. According to Hebrew University, more than 100 million land mines remain buried around the world. Metal detectors do fine with traditional mines, but plastic ones elude them.”

A huge number of ideas to detect and clear mines have been tried. Here are a few:

Mine detection techniques have remained as pedestrian as they were in World War II: soldiers with sticks and serendipity; dogs, who do get killed; and pigs (a talent discovered by a kibbutznik in Israel). The most noteworthy advance in decades had been recognizing the mine-sniffing talents of the African pouched rat.

Now come Hebrew University of Jerusalem scientists, with a truly creative idea, thinking out of the box, or in the bubble or beads:   Bubbles with bacteria that glow blue when they detect vapors emitted by land mines.. even tiny amounts of the gas, and all mines emit such vapors.

       “Inspired by an idea that was first conceptualized in 1999, the scientists engineered   bacteria that fluoresce when they come into contact with these vapors. The human mine detectors don’t have to keep the bacteria on a leash: they can monitor and react remotely. Nor are the bacteria free-range: they are encapsulated in beads that are scattered across the suspect land. The scientists tested the system with a laser-based scanning system, and the mines were found.”

     Prof. Shimshon Belkin was responsible for genetically engineering the bacterial sensors.   The research was published recently in the leading journal Nature.

In a Vacuum of Political Leadership: Can Business Step Up?

By Shlomo Maital

   The Guardian carries an interesting interview with Paul Polman, Dutch CEO of Unilever, global food giant that employs 170,000 and has a market value of some 90 billion pounds sterling.

     He makes a point we have often stressed in this blog: Multiplying global challenges demand global coordination and policies, yet countries increasingly are looking inward, “America First” from Trump is not the only example.    

“Actually, that is one of the key issues in the world right now – the lack of global governance in a world that has become far more interdependent,” he says.

“Some countries have played their role historically, but seem to be falling back to their home base; others have not been able to step up to the plate, claiming developing market status. But increasingly the issues that we are facing – climate change, unemployment, social cohesion, food security – these are issues of global proportions. We are often trapped in short-termism … or other things.

“Many of the institutions that were designed have served us very well, but they were designed in 1948 at the time of Bretton Woods [the conference held in 1944]. It is not surprising that you have now got an Asian Infrastructure Investment Bank and other alternatives because the world has moved on.”

     I wish Polman would create a new “Bretton Woods” – a summit of top CEOs of the leading global companies. If politics is local, business is global. Why not then have global business rethink our policies and global infrastructure, and begin acting to implement them? These huge companies have enormous power, based on the electoral impact of their workers and the funds they donate to political parties.

 

 

Creativity: Can You Use What You Already Have?

By Shlomo Maital  

One of the most powerful tools for practical pragmatic feet-on-the-ground creativity is – to use what exists, to solve unmet needs and unsolved problems.   Joe Dickinson did this.

   The problem:   Lonely isolated older people, over 60 – soon there will be 2 billion of them in the world.

   The challenge:   Find a way to keep in close touch with them daily.

     The breakthrough question: Who sees people every day, or nearly every day, on a regular basis?   Answer? The postman.

       Joe Dickinson, a postal worker in Jersey, a lovely vacation island off the cost of France, had this simple powerful idea.   Use postal delivery people to check on elderly people. Call it: Call and Check.   See if they are OK. See if they need anything or need medical help. Here is a short description:

Call & Check provides a regular visit for people – daily, weekly or as agreed. Our staff will have brief conversation with the customer to ascertain how they are and if they need anything. Working with our customers’ designated contacts, we are then able to relay important messages or requests back to the relevant authority for action. The postal worker is in no way providing medical care or assistance to the customer, we are simply a regular, friendly face that frequently calls and checks, and can raise concerns with relevant third parties where necessary.

        Call and Check has already saved elderly lives.

           Innovator:   Can you use this approach? Can you define a social problem, and then solve it using what exists already?     Example:   India’s Lifeline Express – a medical train that uses India’s extensive system of rails to reach outlying villages and bring medical care to those who have no access to it.

Profit-At-All-Cost Capitalism: The Sad Case of Valeant

By Shlomo Maital

 

   This is the story of a drug company called Valeant, and its CEO J. Michael Pearson, as reported in today’s International New York Times, on a page 1 story by Gretchen Morgenson and Geraldine Fabrikant, two excellent business reporters.

   Pearson was the architect of Valeant’s strategy, that drove its stock price to an astronomical $262,   then saw it crash to $11, and led to Pearson being investigated by the US Senate, along with William J. Ackman, founder of Pershing Square Capital Management, who placed a huge bet on Valeant and lost $ 4 billion; he too is under investigation.

   The strategy?   Rapacious profit-at-all-cost capitalism. Under Pearson, according to the NY Times, Valeant acquired drug makers with drugs that had few or no substitutes in the US, then jacked up the price by 10 times or more and ripped off hapless patients who needed the drug.   Great strategy? Why not, if drug makers are so stupid that they actually share value with ill people and price their product reasonably. Why bother investing money to develop drugs, if you can buy existing drugs and then run them as Economics 101 explains, as little monopolies?   Especially when the patent law makes it legal.

     What went wrong?   A huge public furor arose, politicians got involved, there were investigations, and then short sellers smelled blood and started selling Valeant shares short, putting pressure on the stock and leading to its collapse.

     Here is how Forbes magazine describes Valeant’s price-gouging actions, along with another company Turing:

      “Valeant and Turing bought monopoly positions in old drugs that faced no direct competition in the United States. But they are important medicines. Nitropress, used to treat patients whose blood pressure has risen to dangerous levels, jumped in price by more than three times to $805 per vial immediately after Valeant’s purchase, while Isuprel, which addresses heart rhythm problems, soared more than six times to $1,346 per vial. Turing purchased a 63-year-old anti-parasite pill, Daraprim (pyrimethamine), and took the even more brazen step of inflating its price by more than 5,000 % to $750/tablet.”

     How many times will we see this sad drama repeated? Short-term myopic rapacious capitalism destroys wealth and value massively. In fact, what Pearson did is not capitalism at all, it is simply stupidity, driven by Economics 101.   Count on this happening again and again, until we redefine and rebuild the basic values of true capitalism – creating sustainable long-term value for customers, and hence, for shareholders.

 

How Trump Used Psychometrics to Win

By Shlomo Maital

 

   My friend Einar Tangen drew my attention to this article:

https://motherboard.vice.com/en_us/article/how-our-likes-helped-trump-win

     Here is the jist of it.

  • A psychologist named Michael Kosinski developed a method to analyze people in minute detail, based on their Facebook activity. The technique is known in general as psychometrics: Measuring psychological characteristics from available data.
  • The company behind Trump’s online campaign (a key part of his win) was Cambridge Analytica, a Big Data company, which also worked on the LeaveEU campaign for the pro-Brexit group.   Cambridge Analytica apparently used Kosinski’s findings…
  • How does it work?       Cambridge Analytica “buys personal data from a range of sources”… aggregates it with the electoral rolls of the Republican party, and calculates a Big Five personality profile… digital footprints “suddenly become real people with fears, needs, interests and residential addresses.” Motherboard was told: “We (Cambridge Analytica) have profiled the personality of every adult in the U.S. – 220 million people!”.  
  • An example:   Design an ad based on gun rights.   An image on the left: an intruder smashing a window.       On the right: a man and a child standing in a field, at sunset, both holding guns, clearly shooting ducks.       Tradition, habits, security, family.
  •    “Pretty much every message that Trump put out was data-driven”.         E.g., on the day of the 3rd presidential debate (the one Trump did well at),   Trump’s team tested 175,000 different ad variations for his arguments, to find the right versions above all, via Facebook.       They found what resonated most.       “We can address villages or apartment blocks in a targeted way. Even individuals”.
  • One goal was to “suppress” Hillary voters. How?       Keep left winters, blacks, etc. away from the polls, by (in Miami’s Little Haiti) stressing how the Clinton Foundation failed in its efforts to help, after the Haiti earthquake. These dark posts “can only be seen by users with specific profiles…”.  

 

   Amazing that Trump, who lacks even a computer on his desk, was elected by some very very advanced Big Data methods. Thank Steve Bannon, who is not to be underestimated…ever!

What Happens to the Brain During Creativity?

By Shlomo Maital  

John Coltrane

   At the main bus stop, at my university Technion, there is a set of bookshelves, where people drop off unwanted books and others browse and take them. I’ve put a great many books there and they always disappear quickly.  

   One day this week I noticed some rather old copies of Scientific American. I took two of them, to read while on the bus. One of them had a fascinating article by Charles J. Limb, a surgeon who plays saxophone, does cochleal transplants, and loves John Coltrane. (The article was in the May 2011 issue, nearly 6 years ago).

     Using FMRI (functional magnetic resonance imaging), Limb asked, what happens to the brain when jazz musicians improvise?   Coltrane, legendary tenor sax player, did incredible improvisations.   How? Why?

   Here is what Limb found: “creativity is whole-brain…during improvisation, the lateral prefrontal region of the cortex shuts down (areas involved in conscious self-inhibition, self-monitoring, evaluation of rightness and wrongness of what you are doing). Another area of the prefrontal cortex, medial prefrontal cortex, turns on…this is the focal area of the brain that’s involved in self-expression and autobiographical narrative..it has do to with sense of self.”

     Brief summary? Want to create? Turn off all inhibition, judging, evaluating, good or bad.   Turn them off.   Activate your own self, self-awareness, self-expression… express who you are, what you are, tell your story.

     And Coltrane? “He practiced. He was an obsessive—he practiced obsessively. He was after the ability to have an idea he had never had before…be profound, and be able to executive the idea.”

     John Coltrane was creative, had ideas…but he had technique, he mastered his instrument so that he could effortless IMPLEMENT his creative ideas. You need both. Discovery (creativity). And Delivery (practice, practice, mastery mastery!).

       That, according to Limb, is creativity.

Snap – Netscape On Steroids?

By Shlomo Maital

snap

On August 1995, Wall St. witnessed a near-miracle.   A company called Netscape Communications, maker of the first widely-used Internet browser (given away for free) did an initial public offering of its shares.

     Here is what happened: “The stock was set to be offered at US$14 per share, but a last-minute decision doubled the initial offering to US$28 per share. The stock’s value soared to US$75 during the first day of trading, nearly a record for first-day gain. The stock closed at US$58.25, which gave Netscape a market value of US$2.9 billion.”

     That defying-gravity IPO showed Wall St. it had a sure-fire way to print money – issue shares of dot.com companies, and watch the manic rise print profits for insiders. The bubble burst in 2000/1, and then came a bigger collapse, in 2007/8.  

   Fast forward to the remarkable IPO of Snap Inc. (Snapchat, photo messaging company).

   “Snap shares closed their first day of trading up 44 percent at $24.48 a share, quenching a long drought in the market for tech IPOs.  More than 200 million shares — the entire size of the offering — changed hands over the course of the day, accounting for roughly 10 percent of the total volume of trading on the New York Stock Exchange on Thursday. The stock opened shortly before 11:20 a.m. on Thursday in New York, and started trading at $24 a share, rising 41.2 percent from its pricing at the open. The company, trading under the ticker SNAP, priced its public offering at $17 a share on Wednesday.  Share prices rose as high as $26.05,  and fell as low as $23.50.  The opening price of $24 puts the company’s market capitalization at about $33 billion, about the size of Marriot and Target. Twitter’s market cap is about 11 billion, while Facebook’s is about $395 billion. The young ephemeral photo messaging company posted a $515 million loss last year.

So, a company that lost over half a billion dollars last year is valued by the market at $33 b., equal to the valuation of a huge hotel chain, profitable, or a huge retail chain, also highly profitable.

     Here we go again.

Blog entries written by Prof. Shlomo Maital

Shlomo Maital
April 2017
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