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    • Cold War 2.0 Incoming
      Right, with the ban on Huawei using chips made with American manufacturing equipment (one of America’s last few places of absolute advantage); the bans of TikTok, Tencent and WeChat; the attempt to convince other countries to not use Huawei 5G; the arrest of the Huawei founder’s daughter for doing business with Iran along with the […]
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What’s in my Instapaper queue?

It’s getting crowded in the Instapaper queue.  Time to clean it out.  This is what I’ve found interesting lately:

1.) The Dragons of Inaction is a 2011 paper from the journal American Psychologist listing the reasons behind the resistance to climate change claims.  As you may expect, resistance can be grouped into ideological and non-ideological causes.  One of the most interesting causes is mistrust.  We should expect that the people most likely to benefit from climate change denialism will play on trust issues in their target audience.  The conclusion section is light on recommendations but I thought it would be a good exercise to learn how the Fox News crew might put this information to use.

2.) An Ominous Health Care Ruling is the latest editorial by the NYTimes on the two Obamacare rulings yesterday regarding subsidies.  The editorial board is remarkably frank, given its boosterism for the ACA:

The 2-to-1 decision issued by the panel hinged on how to interpret language in the Affordable Care Act that most experts agree was poorly drafted and would ordinarily have been corrected by a Congressional conference committee. In this instance, there was no conference committee because the law was passed on a take-it-or-leave-it vote in the House to avoid a Republican filibuster in the Senate.

But then it reverts to form at the end by stating that regardless of what Congress did or didn’t do by rushing the bill through, the judiciary has a responsibility to not use ideology as an excuse to take subsidies away.  IMHO, the ACA perfectly demonstrates my former advanced inorganic chemistry prof’s saying, “If you don’t have time to do it right, when will you have time to do it over?” In other words, we are all potentially screwed by the effects of this bad legislation until Congress decides to do it over the right way.  When it has time.  And when it also has the rare astronomical convergence of a filibuster proof majority in the Senate, a majority in the House and a president in the White House who, you know, actually gives a crap.  Maybe some time next century. Maybe that was the plan.

3.) In A $650Million Donation to Psychiatric Research, we find research into the causes and a cure for bipolar disease funded by a billionaire with deep pockets who also has a son afflicted with the condition.  It’s great for people with bipolar spectrum disorder but not so great in that it takes a private person to fund it.  The reason so many pharmaceutical companies are pulling out of psychiatric research is that it’s incredibly expensive and there is an extra hurdle to jump when it comes to the brain.  It’s called the blood brain barrier and it gives drug designers and medicinal chemists fits because only compounds with certain physical properties can cross this barrier and they are devilishly hard to make and get approved.  So, you know, there’s not so much profit in it for Big Pharma.  And now we have to rely on billionaires with a personal stake.  {{sigh}}

By the way, the recipient of this largess, the Broad Institute in Cambridge, MA, is primarily a computational biology outfit.  That will be very useful for tracking down the genetic causes and systems biology associated with bipolar spectrum disorder and schizophrenia but biologists don’t make the drugs.  That’s what medicinal chemists, structural biologists and drug designers are trained to do.  It will be curious to see going forward whether the Broad Instituts recruits more of these specialties or decides to farm them out.  Farming it out would be a mistake, I think, since project teams need to see the same material and work on it together.  On the other hand, if Broad doesn’t mind hiring modelers remotely, I am available.  😉

4.) The Atlantic posted an article on The Dark Side of Emotional Intelligence.  In short, being acutely attuned to the emotional states of everyone around you might be great for salespeople but it sucks for people working in professions that require concentration and contemplation.  For the latter group, paying attention and kissing up to the people around you is a distraction.  The resulting effects on the working environment of those people expected to play the EQ game when they don’t have time for it are predictable. From the study cited in the article:

Cote’s team assessed how often the employees deliberately undermined their colleagues. The employees who engaged in the most harmful behaviors were Machiavellians with high emotional intelligence. They used their emotional skills to demean and embarrass their peers for personal gain.

Seen that happen with my own eyes.  Depressing but all too common, especially in the uber-competitive environments engineered by biz school grads and propagated throughout the industries they manage.

5.) The website, Ask the Headhunter, has a video for those of you who can’t get through the HR filters that you are required to navigate to apply for jobs.  If you are lucky enough to already have a job and haven’t been through this exercise in futility, it goes something like this: You see a job on a website for which you are (probably over)qualified and are directed to the company’s HR application system.  Then you spend hours per application uploading your resume and then reformatting it (god knows why the reformatting step is necessary but the OCR never gets it right.  Besides, didn’t you just upload a copy of your resume??).  Anyway, after you have edited and reformatted and written a brilliant cover letter telling the company all of the reasons why you would be more than perfect for the job, you never hear from them again.  Oh, sometimes you’ll get a form generated reply saying they received your information.

The truth is, there are filters that are set to weed people out and nobody knows what they are.  In some cases, the HR filter is set so unproductively that most applicants who qualify never make it to the resume review round.  That may be why so many employers whine they can’t get good help anymore.  If they would only hire people who could reset the filters for them they might get better candidates.  But to do that, they’d have to reset the filters themselves in the beginning and that takes vigilance, time and probably one FTE. It’s a vicious circle. Nick Corcodilos says to scrap the resume and don’t bother going through the HR application process.  The best way to get a job is to hang around people in your field or the area that you want to get into, and make connections.  In other words, you need to be a human with a face because HR filters do a lousy job of staffing and are probably not worth your time.

6.) Alistair McCauley reviewed the current production of the Bolshoi’s Swan Lake at Lincoln Center.  It’s not pretty but it is a fun read:

At the start of every dance, my heart would lift again, noting some marvelous feature of Bolshoi style. The communicative generosity of manner! The thick-cream legato flow and keen dynamic sense! The juicy red-meat richness of texture! The unaffectedly erect posture of the torsos and their gorgeous pliancy! The easy amplitude of line! The powerful sweep through space! Yet nothing availed. Each dance soon grew monotonous.

I can’t remember, is McCauley the critic who thinks all ballerinas could stand to lose a little weight?  Anyway, I’m not a fan of companies with a lugubrious ballet style.  Give me something livelier, and, er, probably not Swan Lake.

7.) I. Must. Have. This. Desk from CB2.  I am confident that my life and blogging will be improved by it.

And a heads up to you IKEA fans.  The 2015 Catalog is supposed to hit the interwebs tomorrow.  I can hardly wait!

8.) Finally, I am on the third part of the longest Audible book I have ever “read”.  It’s The Last Lion, a biography of Winston Churchill.  It’s excellent and probably more detailed than any biography has a right to be.  Highly recommended.  5 sponges.

So, I ran across a page on some of his predictions and inventions.  For example, did you know that Winston invented the tank and the onesie?  Ok, maybe not his finest hour.  But he was a great futurist.  Check it out.

The funny thing is, Churchill was never a great student but he had a formidable intellect.  He was definitely not Ivy League material in the most 2014 sense of the word.  That would have been a great loss for England if our current standards of performance were in effect then.  He might have ended up writing Op/Eds for WaPo and gone no further in life.

And here are a few Winston quotes for good measure:

“If you’re going through hell, keep going.” (Sound familiar?)

“Success consists of going from failure to failure without loss of enthusiasm.”

“If you have an important point to make, don’t try to be subtle or clever. Use a pile driver. Hit the point once. Then come back and hit it again. Then hit it a third time – a tremendous whack.”

“It is no use saying, ‘We are doing our best.’ You have got to succeed in doing what is necessary.”

“The inherent vice of capitalism is the unequal sharing of blessings; the inherent virtue of socialism is the equal sharing of miseries.”

He made his share of mistakes and was on the wrong side of history as far as women’s suffrage was concerned (they turned out for him anyway).  He failed many times but he learned from his failures and he never surrendered.  Cool dude and an honest guy.  We need someone like him right now.

 

 

 

 

 

 

Dead Space in the Pharma Pipeline

This article is a few months old but just now showed up in my LinkedIn updates.  It’s another indication of disintegration in the pharmaceutical industry as it heads towards the “patent cliff”:

Scientists warn on “dead space” as pharma giants shuns neuropsych:

European experts are sounding an alarm about the recent pullout of GlaxoSmithKline and AstraZeneca from the brain disorder arena.  David Nutt, a professor Imperial College London, and Oxford’s Guy Goodwin are calling for a rapid response to what they term a collapse in R&D spending in the field.

“What we have forgotten, and must not forget, is if we stop this research we will have a dead space of 20 to 30 years before we can re-tool again,” Nutt tells The Guardian. “Despite the public health imperative, not only has EU research funding remained very low, but–even worse–big pharma is increasingly coming to see research into better neuropsychiatric drug targets as economically non-viable.”

That effectively sums up the position of GSK’s Andrew Witty, who has explained that the huge risk associated with developing new drugs for neuroscientists is just too high to justify the investment necessary. The Guardian notes that the average time it takes to develop a new drug for a brain disorder is 13 years-considerably higher than the average program and significantly more expensive.

The article goes on to say that the authors have proposed that pharmas be encouraged to give this area of research to academic labs and that government make an effort to protect small labs and companies who agree to do this research.

The reason why neuropsychiatric medications are so “economically non-viable” is because the body protects the brain from foreign, potentially toxic substances with a physiological feature known as the “blood-brain barrier”.  Basically, there is an extra “layer” of protection around the central nervous system that drugs have to cross in order to reach their targets.  That means, the compounds that might be the most effective have to first be bioavailable to the body and then have to have  certain additional physical properties to cross the blood-brain barrier.  Developing these kinds of drugs is very time consuming and has a high failure rate.  Messing with the brain is not for the faint of heart.  There are specificity issues to deal with as well.  I once worked on a project where the drug was initially developed to target a serotonin receptor in the brain in order to reduce appetite.  It turned out that it also caused severe priapism in primates.  We must be very, very careful or someone’s going to lose a penis.

For those of you who might be hoping for a treatment for Alzheimers, schizophrenia, bipolar disorder, epilepsy or stroke, the authors of this article are saying that the research in these areas are so expensive for big pharma that they are mothballing the projects.  Starting them up again, and finding chemists who understand what it takes to make compounds that cross the blood-brain barrier is going to set back research by 20-30 years.  Then, if a company or academic lab does decide to take this on, they’re going to need governmental protections, to keep them from going under while they work out the kinks.  Presumably, this would include some kind of insurance against the inevitable class-action lawsuits as well as some kind of patent protection.

The patent reform act that was signed recently will probably not be a friend to small labs.  The change from “first to invent” to “first to file” puts a lot of burdens on small labs that may not have a fully staffed patent department to work through a patent application.  That leaves them vulnerable to large pharmas who will make them an offer they can’t refuse.  If I were reforming the patent problem, I would have split off biomedical patents from other patents and then, counterintuitively, extended the patents for new drug entities.  Before you get your knickers in a twist, hear me out.  One of the reasons that drugs are so expensive is because they spend a lot of time in development and clinical trials and those trials eat up the time left on the patent.  These days, the FDA requires more safety data and clinical trials before a drug is approved.  (I *know* there will be some readers who will insist that drugs are fast tracked but they are not paying attention.  Fast tracked drugs are mostly oncology drugs where there is a bargain between patients who are terminally ill who may be willing to forgo the additional safety requirements.  Fast track for all other drugs is very rare)  The longer the drug sits at the FDA, the greater the potential high cost to consumers and marketing executives, seeing an opportunity to increase share holder value, may pad that price even more, using the FDA holdup as an excuse.

Pharma is also not well served by the frenzy of the financial markets to produce higher profits every 3 months.  When push comes to shove, the human body will do what it damn well pleases.  You can’t force Mother Nature to perform on a quarterly basis.  See Derek Lowe’s post on GSK’s mystifying new scheme for creating a pharma division with a racecar fuel manufacturing facility.  We have no idea what GSK is thinking but we are aware of some computer chip manufacturers complete cluelessness when it comes to drug research.  You can’t research a drug the same way you research a chip.   And MBAs who do not understand their business will do dumb things when they are under pressure to produce profits.  Biomedical research is unlike any other form of high tech research.  You can’t pair the two and expect that the cells that the biologists are working with will suddenly get a clue and get with the program.  And this is why the patent problem is also different for the pharma industry because shortened research cost recuperation times leads to a lot of very stupid short-term thinking.

If I were to reform patents, I’d stop the patent clock while the drug was going through the clinical and approval process and resume it after approval.  Then make a deal with the pharma industry to ease up on pricing in exchange for longer exclusivity.  This accomplishes two goals: it takes the pressure off of pharma to price the hell out of the drug and it steers them back towards long term planning.  If they know the patent cliff isn’t looming a few years down the line, the pace of mergers and restructuring might slow down and research would have some breathing room to get back to business.  It’s a theory.  There’s always a way for the financial class to game the system so thinking this through carefully and plugging the loopholes would be very important.  But that’s what I expect from my congressmen- careful, meticulous examination of the problem with reasonable solutions.  Changing the first to invent to first to apply rule did not do that and may have inadvertently exposed entrepreneurial labs to additional risk and expense.  Well, inadvertently to Congress; opportunistically to the big pharma vulture capitalists.  Hey, it’s a business.

Anyway, it’s something to think about.  It’s not just CNS drugs.  Antibiotics are also losing their shine with the big pharma giants.  Too many lawsuits.  Oh, well.