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Need Yves Smith’s analysis of new Pfizer hostile takeover of Astra-Zeneca

Derek Lowe at In the Pipeline has a post on Pfizer’s hostile move on Astra-Zeneca:

What the hell is Ian Read thinking? Pfizer is apparently going hostile with their attempt to buy out AstraZeneca, all but ensuring that the deal, if it goes through, will take place at the highest price and in the messiest fashion that it possibly could. And for what?

If you’ve been following Pharmageddon from the beginning, you will know that Astra-Zeneca’s fall off the “patent cliff” was one of the steepest in the industry.  The patent cliff is the term used in the industry that refers to the expiration of patents for the major blockbuster drugs.

Patent Cliff by company since 2010.

 

Weirdly, most blockbuster patents have expired within the past decade because they were discovered in the 90’s, the golden age of drug research.  If you’re wondering why your blood pressure meds are suddenly so affordable, that’s why.  They’re generic now.  Pharma can’t make as much money off them anymore.  Great!, you say.  And it probably is great, to some extent.  The problem is there is not a lot in the pipeline to replace them, that is, if you’re interested in more effective drugs with fewer side effects.  There are several reasons for this that I’ve discussed in previous posts but the primary cause is NOT for lack of trying.  Researchers have seemingly endless dogged determination to preserver in  the face of failure after failure.  The problem is that research has to deal with *two* impossible systems: the complex biology and the self-serving, clueless managerial/finance class.  And the underfunded and politicized FDA.  Make that THREE impossible systems.  And the class action law industry.  FOUR! It all adds up to unnecessarily and ridiculously expensive drugs.  But I digress.

So, according to Derek, Astra had some really rough years, laid off a ton of people in Delaware and all around the world, but hired a new guy in 2012 to turn the ship around and has plans to consolidate a tiny fraction of their research unit in Cambridge, MA where no one really wants to work because it’s a.) expensive, b.) a pain in the ass commute and c.) an insecure career environment for researchers.  MBAs really are a bunch of status snob lemmings, I swear.  Or magpies chasing the latest shiny thing.

My bad, that’s Cambridge, UK where AZ wants to set up its stripped down R&D division.  It’s probably just as attractive to the relocated researchers (You happy few!  You band of brothers!) as the American Cambridge.

Derek makes a good point in that Pfizer has a lot of money to spend on the small, nimble biotech startups that MBA types have told the analysts are supposed to be able to generate a s^&*load of drugs to inlicense.  They’re like unicorns, these little startups, or like perfectly elastic collisions of particles in a box.  Theoretically, they exist but in the real world?  ehhhhh, not so much.  Drugs rarely emerge from these tiny incubators fully formed because, helloooooo, Silicon Valley, drug discovery is NOT like writing code for a new Facebook.  But you’ll find out in the next couple of years.  Just sit in on one of the project teams while the biologists drone on and on and on about how much to tweak the components of their confirmatory and cell based assays to make them reproducible and it will quickly dawn on you that drug discovery makes coding look like Chutes and Ladders.  Even so, we’ve got to wonder why Pfizer is choosing to forgo spending some of their billions on the biotech startups in order to sit on a pile of cash.  Where is the drive for innovation we’re always hearing so much about?

Anyway, where was I?  After pondering the problem for awhile, Derek hypothesizes that Pfizer is buying Astra-Zeneca, a foreign owned company, to hide its taxable profits from the US government.  Or the British government.  It’s like some British, Swedish, American threesome, which initially sounds like a good time for everyone except the citizens who actually count on corporations to respect them. It’s a rather strong accusation but Derek says he never wants to work for Pfizer anyway.  That’s Ok for him but my pension was acquired by Pfizer when it gobbled up Wyeth and then proceeded to lay off every one of the people I used to work with.  I’m kind of concerned with this wobbly third leg of my rapidly disappearing retirement stool so if Pfizer is up to something, I’d like to know what the heck it is.

The remaining survivors in research at Astra-Zeneca can see what’s coming.  They must be busily rewriting their CVs and networking instead of finishing that reaction or fishing the crystals out of solution to send to the synchrotron.  What a lovely way to spend your hours in the lab.  And the industry wonders why there is nothing in the pipeline after 20 years of this crap.

What this research project team really needs is a financially nerdly Yves Smith type who can look at the details of the proposed takeover and report back in a meeting to tell us what’s up.  More to the point, what does the UK’s new tax rates for foreign profits say about whether the conservative government is trying to make Britain into a sleeker global tax haven?  I’m just a chemist.  Money is not my area of expertise.  This project team needs a finance specialist.

 

 

Recording confirms that the sexiest thing in Don Sterling’s pants is…

his wallet.

 

Meanwhile his takers, er, his team, has signaled their disapprobation by wearing their red shirts inside out.

Sounds like a plan.

 

YoungHouseLove, Lorde, TinyHouseSwoon, My Girls

Living with faux brick and feather finish concrete over laminate countertops in Richmond

Yesterday, Sherry Petersik, blogger at the wildly successful DIY/Design blog YoungHouseLove wrote the unthinkable in modern day America.  She and her husband John are cutting back on posts and projects.  For those of us who have looked forward to their posts and their inventive use of painted ceramic animals and feather finish concrete, this comes as no surprise.  The Petersiks are cursed with an excess of talent.  There’s something demonic about it.  I mean, it’s like they’re not even trying.  (Um, actually, it seems like their “Hey, why don’t we put on a show!”Andy Hardy-esque enthusiasm might be wearing them out a bit.)  And yet, even though the rest of their world has been throwing project after project at them and probably littering their email boxes with offers to turn them into the biggest commercial successes since Martha Stewart, they’ve decided to pull back and NOT be rich and famous.

Weird.

Well, it could be the recent addition of new son Teddy or that they want to spend more time enjoying the quirky charms of daughter Clara, and Burger, their chihuahua.  Check out this post of the anti-super super couple for a better idea of who they are:

But something tells me that the Petersiks, who abandoned successful careers in advertising in New York City for a more provincial, slower life in Richmond, VA, are making a statement about who they are and what they aspire to be.  They’re about making things work with what they have, finding beauty and art in inexpensive things, and turning down those lucrative business propositions for something more grounded.  They are saying they don’t need to be rich to be happy and they don’t envy the oligarchs.  Really, you Davos, champagne swilling set, they don’t want to be you.

Without even realizing it, I’ve started to adopt a YoungHouseLove philosophy to my house as well.  Like them, I bought a fixer upper last year and I’m really delighted with it.  I just renovated my kitchen for less than $5000, but if it had been solid construction like the one in the Petersiks’ house, I might have just painted the sucker instead of replacing everything and spent much, much less.  We do have the same faux brick floor, however, but mine doesn’t have gouges in it like theirs.  And like them, I decided not to replace it right away.  I made it work.

I also started filling in the empty sunroom that I needed to have rebuilt last year (it was an eyesore.  The neighbors are giving me tons of positive reinforcement about it and the garage door).  But I’m shopping my own house for stuff to put in there, like an old camelback sofa, the wicker chair from my bedroom and the area rug that used to be in the kitchen.  It turns out I have more stuff than I realized and I can repurpose it with a little bit of imagination and paint when necessary.  I’m about to chalkboard paint the walls in the tiny half bath downstairs and leave a cup of colored chalk so guests can leave their “for a good time call Jenny” graffiti on the walls.  Why not?

I’ve been noticing that it’s not just the Petersiks that have decided to forgo the McMansions and the high stress jobs.  The Tiny House movement is amazing with its emphasis on sustainability, debt free lifestyle, inventiveness and living with only what you absolutely need attitude.  For example, I could be quite comfortable in the 210 square foot Minim house. The layout is genius:

Then there’s Lorde with her message of not being impressed with all the trappings of fame and success.  Her songs are about her friends and hanging out together and having an interior grace that is independent of gaudy, modern Versailles externalities.  What you have does not define who you are.  I was impressed with her decision to not to tour with Katy Perry.  She could have cashed in big.  She decided that wasn’t what she was about.

What’s disconcerting to me is the uncomfortable feeling that the marketing industry may already be furiously calculating how to capitalize on this stripped down, anti-materialistic trend.  “Less is more” means the moneyed class has less control and they’re not going to like that.  Picture the screaming, flailing swamp monster on fire, refusing to die without a fight.  But more seriously, in the long run, it’s not good for the American economy if everyone cuts back, repurposes and sustains, even if it’s great for your mental health and physical well being to forgo the stress for a more hobbit-like lifestyle. It would have been great if this country had focused on more social and forward looking policies like less oil dependence, better health care policies, affordable education and family friendly initiatives.  But the bonus class appears to be committed to a short term, eat the seed corn working model and is determined to extract every last penny of disposable income from our wallets and bank accounts.

The return to living within you means is a reasonable and self defensive response from several generations who no longer want to be considered crops ripe for harvesting the minute they start to make a living.  It’s not opting out.  It’s exercising personal agency and making a choice.  We don’t want to be treated as an exploitable resource anymore or the anonymous, depersonalized set of data by which other people become irresponsibly rich.  We’re not interested in 40 years of an insecure employment environment, a measly 2 weeks of vacation per year and no time with the kids.  It’s stressful and unhealthy for us and the environment.  Life is too short to be slaving away for ungrateful rich guys who appear to lack the consciences to invest the money they are extracting to make the world a happier place.  Giving up the best years of our lives so they can sock trillions of dollars in tax free profits in offshore accounts is increasingly unpalatable and we’re not interested.

N’est-ce pas?

 

 

 

Non-fiction day: The Divide and The Lucifer Effect

I’m not quite finished with Matt Taibbi’s new book, The Divide: American Injustice in the Age of the Wealth Gap, but I thought I’d review it now because, a.) I’m pretty sure of my impressions of the book and b.) it should be read in conjunction with another book, The Lucifer Effect: Understanding How Good People Turn Evil by Phillip Zimbardo.  I dunno, maybe I should read the Taibbi book to the end to see if he makes the connection but I’m beginning to get outrage fatigue, which is why it’s probably a good idea to read the more clinical prose in Zimbardo’s book to gain perspective.

So. Much. Morality.

The premise of Taibbi’s book is that the justice system is divided into two parts in this country.  If you are a member of the bonus class or oligarchy, your possession of the One Ring makes it nearly impossible for the justice system to prosecute you.  You’re invisible to the powers of accountability for one reason or another.  On the other hand, if you are a member of the working class, that is, anyone not living off their investments, the justice system can make your life a living hell.  Just breathing wrong can get you into trouble and that trouble is excessively punitive, relentless, expensive, arbitrary and seemingly endless.  It doesn’t take much to fall down the rabbit hole but it takes even less if your are a member of a minority population.

Sidenote: We have experienced this in our own family when a cousin’s persistent drug problem lead to direct interaction with the justice system.  He needed rehab- quickly.  What he got instead resembled Les Miz.  In the end, the legal system and it’s self-replicating fees, coupled with unmerciful punishment of every imaginable variation, put him in a hole he could not climb out of, made him homeless, broke and despondent.  He committed suicide.  So, you know, we definitely know what Matt is talking about. You don’t have to be black or hispanic. All that is required is that you have no money and live in a country where the public has been trained to be completely unsympathetic to what is happening to you.

Taibbi alternates the book with stories from each side of the divide.  We swing from bankers on Wall Street who got away with murder to “stop and frisk” detentions of young black men who are just standing outside their apartments at the wrong time.  Where the justice system seems willing to take a “boys will be boys” attitude towards the bankers, it comes down on the loiterers with a vengeance, depriving them of their dignity in the courtroom and subjecting them to endless hours of waiting around, mounting fees and coercion to plea to crimes they didn’t commit that ultimately deprive them of their right to public housing and student loans.

Taibbi doesn’t write with the same snap and clarity as Michael Lewis or Neil Barofsky  when describing the machinations of the Wall Street criminals.  His prose tends to meander, feels insidery (is that a word?) and it was difficult to follow who did what to whom.  This only pertains to the case studies in the upper justice system but I think his editor should have pulled him aside and asked him to tighten these sections up. He could never have gotten those case studies published in the kind of peer reviewed journals the science community is subjected to. Both Lewis and Barofsky have demonstrated that complexity doesn’t have to be confusing, even in an audio book.  But if you’re going to plow through Taibbi’s book, you’re probably better off getting the ebook version so you can make notes, leave book marks and create a flowchart.

On the other hand, Taibbi’s case studies of what happens on the bottom half of the justice system are easy to understand and  heartbreaking, probably because the infractions are so minor but the reaction is so severe.  It’s like the American justice system is chock full of turbo charged law and order types who carry out punishment with ruthless and brutal inefficiency.  And there was something about depersonalizing experiences of the victims and the anonymity of flawed computer systems of the justice system that reminded me of the Stanford Prison Experiment that Phillip Zimbardo carried out in the 70’s.

In case you aren’t familiar with the experiment, Zimbardo, a psychology professor at Stanford, wanted to replicate the experience of prison in order to figure out how the accused reacted to incarceration and depersonalization.  So, he recruited a couple dozen students to take the roles of prisoners and guards.  He randomly assigned the students to one of the groups and had the prisoners arrested and processed by real police.  In the makeshift prison, the prisoners were stripped of their clothes and given numbers instead of names.  The guards hid behind mirrored sunglasses and were given very few instructions. The warden was hands off.  Well, it didn’t take long before the guards started exercising authority and the prisoners started to crack.  We’re talking days.  It turns out that when one group of people is given all of the power and another group of people is subjected to that power, depersonalization and lack of oversight, it can lead even the blandest guy on campus to become indistinguishable from one of the guards at Abu Ghraib. The guards imposed capricious, humiliating and sadistic punishment while the prisoners became more and more despondent and stressed.  Zimbardo went on to testify as an expert witness in the Abu Graib trials.  He concludes that even the most decent, moral people are capable of evil behavior when the situation is right.  Group dynamics, conditioning to authority and dehumanization contribute to the kind of evil we saw at Abu Ghraib and, it seems, the excessively punitive experiences of the victims in the lower half of the American justice system.

The more I read Taibbi’s book, the more I was reminded of Zimbardo’s book.  So, I recommend you read Zimbardo’s book first and follow it up with Taibbi’s.  In fact, that’s the only reason I would recommend Taibbi’s book.  Without a proper context, it lacks the force it needs to land a powerful blow.  And that’s why I’m going to finish it even though the stories of “getting away with evil” followed by “getting away with nothing” are somewhat monotonous.  Taibbi might make the connection in the final chapters and have that eureka moment that will make it all worth while.  But I’m almost done with the book and see no evidence of it yet.  I’m afraid that the lefty community will miss the larger point that could propel it out of its fecklessness.  Instead, it might fall back on the “Bill Clinton is to blame for all of this!” crap they’ve been mindlessly vomiting for the past decade (as if Newt Gingrich and his Contract On America never existed {{rolling eyes}}).  What a horribly wasted, missed opportunity to see the world as it truly is.

3 Sponges for The Divide

4 Sponges for The Lucifer Effect (it can bog down with too many details in the first part)

PS. The left should study part 2 of Zimbardo’s book to understand how to resist situational influences.  It’s going to come up again in 2016.  Let’s not get fooled again, m’kay?

Oh, and here’s a concept that we should all learn about: malignant narcissism.  Don’t throw it around indiscriminately though.  It’s the kind of thing that Fox News and Rush Limbaugh types will seize on and dilute.  (it’s what they do)  But the next time an oligarch whines about how the rest of us are mean to them and envy their wealth, think about malignant narcissism.  They’re on the spectrum.

 

 

 

Does anyone know how to get in touch with Laura Poitras?

I have a kid who is taking a gap year and wants to learn about documentary film making.  She’s multilingual, speaks German, French, some Italian and is teaching herself Mandarin. Also, was enrolled in Stanford Online High School for some of her classes. She’s a weird kid with many talents and probably destined to take an unconventional path to professional success so I need some advice on how to steer her in the right direction.

Any help is gratefully appreciated.

Krugman and I differ on Obamacare

This is sad.  I really like Paul.  We agree on so many things.  He’s one of the few people who is getting a clue about the myth of structural unemployment.

But with Obamacare, he’s hopeless.

I think it has to do with his own social isolation.  He lives in Princeton surrounded by some of the most successful individuals in the world.  Of course, all around him is the detritus of 6 years of dismantling of the R&D industry.  He only has to cross Route 1 to visit the now shuttered lab where I worked for 15 years. Some of the smartest people I know are having a really hard time figuring out what just happened to them.  But it’s unlikely that Krugman knows many of them, or any of the less accomplished people I know.

Here’s the part of Paul’s latest Conscience of a Liberal post on Obamacare that I resent most:

The current state of public opinion on health reform is really peculiar. If you’ve been following the issue at all closely, you know that the Affordable Care Act is one of the great comeback stories of public policy: after a terrible start, it has dramatically exceeded expectations. But hardly anyone seems to know that.

It’s easy to understand how that happens for Fox-watchers and Rush-listeners, who are fed a steady diet of supposed Obamacare disaster stories.

Um, I HATE Fox News and Rush Limbaugh.  I consider them to be on the same par as pneumonic plague.  They spread misinformation quickly and the effect is always malignant.  I don’t watch cable news of any kind and I don’t listen to Rush.  So, where could I have possibly gotten the crazy idea that Obamacare is a disaster waiting to happen??

Maybe it’s from my own data and observations.  Maybe it’s because the plans are not so great for the price.  Maybe it’s because some of us could afford the lousy premiums if we could get a subsidy but our incomes are too low to qualify (could someone please explain how that even makes sense??).  Maybe it’s the persistent feeling that Obamacare is leading to a less secure job market.  Maybe it’s because for some of us, it’s a choice between cashing in some of our IRA and facing a steep tax penalty to pay for our premiums or being forced into Medicaid where the state may collect our estates from our heirs when we are dead.  There are a million reasons why Obamacare might not be working so well for the rest of us, 40 million approximately.  If Obamacare is only reaching 7 million new subscribers, doesn’t that leave most of the 47 million uninsured still uninsured?

Here’s my take on Obamacare: It’s full of poison pills.  There’s just enough in it to help people with pre-existing conditions and some self-employed people to thrill the cockles of the liberal’s heart.  For everyone else, cost controls are not in place, there are no mechanisms to force competing carriers in a local market to cooperate with each other leaving the unsuspecting facing steep out of network costs, the unemployed are still mostly not covered (and they can’t afford the premiums anyway without a subsidy) and to get any kind of public option, aka Medicaid, you have to give up nearly everything you own and have spent your whole life working for.

This is not a good plan, Paul.  Most people do not live in Princeton or NYC.  They live ordinary lives with ordinary wages and this plan seems to have bypassed many of them.  Obamacare was cobbled together by a chief executive who seemed to want to wag his penis around instead of actually pushing for a well crafted piece of legislation.  Then it was severely compromised by Congress, first by Republicans who are malignant narcissists and then by Democrats who repeatedly sold out their constituents in a desperate attempt to prop up a guy who was not ready to be president.  Why the push to ram this extremely flawed piece of legislation through so quickly?  Why was it more important to save Obama’s ass than to ask him to do a good job?  Why aren’t enough liberals asking those questions?

Don’t insult us, Paul, especially those of us who are die-hard liberals who find the right wing utterly repugnant.  It’s not going to make Obamacare better and won’t help the party.  It reminds me of the days when anyone who saw through Obama in 2008 was called a racist.  It’s not fair and it’s beneath you.

“Keep Going”

The kitchen is painted.  I’m going to hurt the person who used oil based glossy paint on the walls.  The first coat of Zinsser primer peeled off.  That’s right.  The primer peeled off.  (Yes, I checked on the oil/water-based compatability first.  It didn’t matter.) We had to scrape the walls down and start over.  Grrrrr.  But it’s done now and I’ll post some pics soon.  It’s an amazing transformation.  There was a little gem of a kitchen underneath all that gloomy paint and broken cabinetry.

 

 

Fully Raw Cannibals and My Obamacare Nightmare

Re: Conservative reactions to marriage equality, Atrios wrote the following last week:

Marriage equality was supposed to be a “conservative” gay rights issue. And, yes, more lefty queer people (speaking generally) weren’t initially thrilled with it becoming the central gay rights issue of our time. As homophobia is the last truly acceptable bigotry (deeply held sincere beliefs!!!), conservatives were never going to be on the correct side of that issue, no matter how many times Glenn Reynolds tells us that Dick Cheney was a gay marriage pioneer.

Unfortunately, homophobia is not the last truly acceptable bigotry. It is far more likely that fully raw cannibals will achieve acceptance and equality before women do.

***************************************

Now that Sebelius has taken the fall for the fiasco that is Obamacare, I thought I’d relate my own experience with it. Disclaimer: I am not a Republican. I don’t hate Obamacare because it is a government program that saps “freedom” (aka tax money) from Jahb Creaturz. No, I am in favor of a national health care policy that uses the best practices that other industrialized countries have put in place. You know, universal mandates for individuals AND employers, cost controls on the medical industry, public options. I was brought up on military medicine and if it was good enough for my sister with chronic severe asthma, by golly, it’s good enough for me. I don’t need frills.

Anyway…

I recently attended a younger cousin’s birthday party. My relatives sat around and compared plans. This group was a mix of ages, employment situations, number of dependents, personal wealth. The bad news for the Democrats is that no one likes Obamacare. Not one of them. In Pittsburgh, the effect of Obamacare is pronounced because two major insurance carriers in the region are battling and one of them, UPMC, refuses to contract with Highmark BC/BS. That leaves Highmark customers scrambling to find new doctors and praying that if they do have an emergency, they don’t get carted off to one of the ubiquitous UPMC hospitals where they will get socked with a massive out of network price structure. They played nicely before Obamacare but no more.

The problem of insurance plans is particularly acute for those of us who fall into the precariat class and Obamacare falls severely short there. Let me explain from my own experience.

Last year, I got a full time job. Unfortunately, it was a temp position. Temp positions mean no benefits and because it was pre-Obamacare, I paid premiums that were out the wazoo. Because it was a position in an academic lab that was facing economic stress from the sequester, it only lasted until December. Thank you, House of Representatives, Senate and Executive branch. At that time, I could no longer afford the $992/month premium on my health insurance policy. Fortunately, my now non-existent salary meant that kid now qualifies for Medicaid. Ok. Kid taken care of. Great. Now for me.

I went on the Obamacare website and looked for a new policy from my existing carrier. By the way, my carrier called me to tell me the “good news!” that due to Obamacare, they could shave the cost of my old policy down from $992/month to $750/month! Isn’t that great?? The new policy came with supercool new features too. I tried to explain to the customer service rep that I was between jobs and $750/month for a healthy person my age was out of the question but I don’t think she was really listening. I decided to try for a subsidy.

On the healthcare.gov site, I saw some policies in the $400-500 range with reasonable $1000/year deductibles. Great! With the amazing subsidies I’ve been hearing about, I should get a pretty reasonable rate. But I found that there’s always a glitch to these sites or something that needs to be explained to a real person so I decided to apply on the phone instead. This was a mistake.

The navigator asked me questions about my income, (um, non-existent? but only temporarily) and started going through the plans. They weren’t anything like the ones on the website. They were more expensive, had higher deductibles and even the silver plans sounded much more like the bronze plans. It was like the online site and the phone assistance sites were totally different. He quoted me a plan that was similar to the one I already had but it was a more restrictive HMO and the deductible is $3750/year. This was a silver plan. I asked him the price and as we were talking the price of the plan went up. Yeah, it was like buying a plane ticket. The price was changing before his eyes.

Then I asked him what kind of subsidy I was going to get. The answer: none. I was startled. Why am I not getting a subsidy?? Because, he said condescendingly, you don’t have an income and aren’t paying taxes.

I have to stop for a second, oh best beloveds, because I suddenly became livid remembering the decades past where I paid more in taxes in a year than I expect to make in income this year. That really scorched my oatmeal. Apparently, to this smug asshole, I am just a deadbeat.

Then he recommended that I just pay the penalty and skip signing up for a plan. That made me really mad. So, now I am going to be a burden on the taxpayers if my conversation with this navigator gives me a stroke and I end up in a UPMC hospital.

I considered my options. I don’t want medicaid for myself because I don’t want my heirs to end up penniless when the state of Pennsylvania swoops down to recover assets from my estate to cover the medicaid premium. This scenario reminds me of the starving Irish who had to give up the last quarter acre of land before they could get food in a workhouse. I worked very hard for decades for the house that I have. I do have money from the sale of my house in NJ in savings but due to the nature of the job market, I have to hold on to that money to pay for the now perpetually temporary nature of making a living. I have TAXES to pay to my municipality for trash pickup, libraries, roads and schools, all of which I am happy to finance.

I reluctantly signed up for the $500 plan. Then I found a job. BUT it’s only part time and, of course, it doesn’t come with bennies. I don’t know if I can get a subsidy now and until my job situation improves, I’m very reluctant to pay the premium on this crappy plan. I am now without health insurance for the first time since 1986.

But wait! There’s more!

It turns out that temp jobs and part time work is very in fashion this year. It is extremely difficult to get a full time job with benefits. There are such jobs to be had but getting through the HR filters is like tilting at windmills. (If anyone in the Pittsburgh area has an opening, let me know. I have great references.) I think I got my current part time job because I aced the online assessment test. Unfortunately, not enough sites have such assessment tests so we are forced to mind read what most job posters have in mind.

So, my relatives and I compared plans. It turns out that I have the worst plan at the highest price. One cousin had to change her doctors completely. Another cousin has a serious heart condition but hasn’t landed any work yet, so, no coverage. When his prescription from another state expires in August, he’s screwed. Another cousin just lost his job. He’d been working for 6 months but just when his health benefits were supposed to kick in, he was laid off. How conveeeeenient. Ironically, it is my self-employed cousins who have the best policy. We share the same insurance carrier but, for some mysterious reason we can’t figure out, he pays something like $450/month for 4 people and has a low deductible. It makes me wonder how the rates are determined.

The relatives that are doing well under Obamacare are the young, single male relatives. Their rates are something under $100/month. The ones who are doing the worst are the ones 45-65 and who don’t have steady jobs. The number of relatives with crap jobs is steadily rising. If you own your own business, rates seem to be fairly reasonable when obtained directly from the carrier.

And here is where the rumors start. We are all convinced that the reason there is so much part time and temp work with impending layoffs just when you reach the bennies mark is because employers do not want to have to pay benefits and Obamacare means they don’t have to. The mandate only applies to the individual. It won’t kick in for employers for another year- if ever. BUT if you can only get part time and temp work, you do not have the money to pay for the premiums. It’s a catch 22 scenario.

Was there no one running the models when this law was written??

I really wish Paul Krugman would stop crowing about Obamacare. It’s a conservative Republican plan passed by Democrats and it now has a “liberal” sticker on it, whether it is deserved or not. It has opened the door to a race to the bottom in terms of benefits and it’s going to damage the Democratic party. It was an ill considered, poorly implemented plan with long ranging consequences to the working class (that is, everyone not making an income from their investments). AND since I read the new Michael Lewis book on compromised stock exchanges, it has dawned on me that the health care exchanges are equally prone to exploit the unaware. We don’t know what our neighbors are getting in terms of plans but it seems like each premium is calculated to optimize profits for someone.

You don’t have to be a Republican to hate Obamacare. Democrats should be very afraid.

 

 

 

 

Chickens…Roosting…Palbociclib (slightly geekish)

Palbociclib. Who names these things??

See poll below on job posting at the NYT.

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Pfizer recently announced a new drug for the treatment of cancer.  When I saw the article on the NYTimes, I immediately recognized it as a kinase inhibitor.  That’s a class of proteins I worked on in my former life.  There are a bajillion of these little suckers in the cells and they fall into different categories.  They’re important to cancer research because they are some of the culprits that go awry and cause uncontrolled cell growth.  I have never worked on the particular kinase that Pfizer targeted with Palbociclib but just looking at the structure of the drug told me a little bit about how this new drug worked.

First, all kinases have a “hinge” between the two lobes of the protein.  It’s where ATP binds in the native state so that’s where most drug discovery efforts go first to design a drug to block the interaction of ATP with the hinge.  Some drugs bind directly to the hinge in a manner similar to ATP.  I haven’t seen the binding mode of this particular drug so I don’t know that it is a hinge binder.  There is a significant limitation to developing hinge binders and ATP competitive inhibitors: if every kinase has a hinge, isn’t it just as likely that your drug will affect more than one kinase?  Yes!  This is called a selectivity problem and it’s a common obstacle to overcome in kinase projects.  The likelihood that your drug will hit something else that it shouldn’t is higher with ATP competitive inhibitors.  Drug design in this area requires precision.

Second, the article says that the effect of the drug is nothing short of amazing – at first.  Unfortunately, survival time is not significantly increased for the patients.  Now, why is that?  There could be a number of reasons.  The cell is really complex and has a lot of moving parts and cancer cells have a tendency to pump drugs out of themselves.  If you know of anyone who’s been on multiple rounds of chemo, it’s probably because the cells have been able to become resistant to the first line of defensive drugs.  But there are other possibilities  besides the cell pumping the drug out.  The lack of selectivity could be affecting a closely related kinase directly upstream of the kinase that is targeted.  Or it could be that the inhibition of the kinase you are targeting causes the upstream kinase to overcompensate causing up regulation (over expression) of your targeted kinase, which kind of defeats the purpose.  So, you may get some real quality time with your family for most of the length of the time of your treatment but then the whole thing goes FUBAR very, very quickly.

Sound complicated?  That’s because it is.  And that, oh best beloveds, is why cancer is so damned hard to cure.  There are multiple moving parts in the cell and they play with each other in complex ways.  It makes high frequency trading flash bombs on the stock market look simple by comparison.

There are some other interesting features of this drug structure.  I see that it has a protonated nitrogen in the piperazine, which is likely making a H-bonding interaction with a carbonyl or carboxylic acid at the lip of the binding site under the glycine rich loop.  I find the cyclopentane ring intriguing.  I’d love to see the structural biology related to this series to see if I could tweak the residues in the glycine rich loop close to the hinge or push the gatekeeper residue to open up the back pocket…

Oh, wait, that’s right.  The industry laid most of us off, “because we are too menny“.  And besides, I don’t have a PhD and, therefore, I am unemployable in the area that I have decades of experience.  Oh well.

On the other hand, it’s a bit weird to see that in the 3 years since I worked on drugs very similar to this one, there hasn’t been a lot of progress.  It’s very likely that Pfizer has already moved on to a new series or maybe it just gave up on this kinase and this is the best you’re going to get so they decided to stop beating on it and develop this lead.  Hard to say.  One thing is for sure.  Cancer patients make very good customers.  They’re desperate, willing to sell their first born for a potential cure and they aren’t likely to sue you for side effects. So, many companies have decided to focus on cancer and orphan drugs, another potentially lucrative area, while abandoning less profitable areas like antibiotics and CNS drugs that come with the tricky blood-brain barrier problem.

Billionaires are starting to get into the act now.  The high tech billionaires seem to think they can apply the lessons learned from Silicon Valley to the biotech industry.  Yup, just make the whole process of drug discovery more efficient so it can go faster.  Or something.  Just ignore the complexity of the cell.  If we incentivize the geniuses, they will be stop dawdling and get the drugs to market.

Over at In the Pipeline, Derek Lowe’s most excellent blog on the ups and downs (mostly downs) 0f working in pharma R&D, I found a link to a recent article in Forbes by analyst Matthew Herper called “Three Misplaced Assumptions That Could End the Biotech Boom“.  The biotech sector has suffered a shock lately.  It seems like investors are having an “Oh $#*^!” moment as they are starting to realize that outsourcing everything for shareholder value, hiring all of China and India with all of the rapid turnover and falsified data that goes with it, and pushing the small pool of brilliant geniuses in Cambridge and San Francisco to “go faster” isn’t working very well.  The failure rate of drugs advanced for approval is still something like 90%.

Herper cites three reasons why biotech is suffering, the most important one is that in spite of all of the shareholder, billionaire and MBA interventions, the decline in R&D productivity hasn’t slowed.  I’m going to guess that this is directly related to the new revolution we are facing in biology.  The more we know, the more complex the system has become.  It is going to take a lot of time and many minds to sort through all the data to figure out how best, and safely, to put it to use.  Short term profit making is incompatible with this kind of R&D research.  Investors are going to have to sink a lot of money into the system and wait a relatively long period of time for results.  There are no shortcuts, as many of them are discovering.

Duh.  We could have told them that before we were laid off en masse.  What a shame.  All those millions of hours of experience in hundreds of thousands of researchers have been sitting on the shelf for several years while the billionaires attempt to reinvent the wheel and the MBAs apply the latest schemes to split up the R&D units and have them all compete with each other in order to maximize shareholder value.

{{sigh}}

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In other news, the kitchen is almost done.  I’m painting, Ok??  I have to paint over high gloss oil based paint (curse the former owners).

But while I was procrastinating, I found a very interesting link to a job opening at the New York Times in my Twitter stream. It’s for a “Writer, Opinion App Job”.  Except for the preferred three years of journalism experience, I could do this job.  Should I apply?  Take the quiz.

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And now for something Hot and Naughty from Titli Nihaan:

 

 

 

Stabbings in Murrysville

Murrysville is about a 15 minute drive from my house.  It’s the scene of a stabbing rampage in a high school today.  Pretty terrifying.  (We don’t live in Murrysville’s district.) When Brook started school here last fall, it was at a brand new, beautiful suburban high school – with metal detectors, hand searches and wandings at each entrance.  Imagine having to pass through airport security every morning.  Yeah, not fun.

But it is pretty safe, no doubt about it.

It’s interesting that the suburb where I chose to live in Pittsburgh has a reputation for having a bad school district.  I haven’t found this to be true. The guidance department is superb, compared with the mean and nasty guidance department I dealt with in NJ.  The crime rate in my district is actually lower than in the city of Pittsburgh.  I checked before I bought the house here.  The problem is that the worst section of the city is adjacent to my district and the students are bussed in.  Actually, bussing in is not the problem.  These students have as much of a right to a decent education as anyone else.  But poverty and a less than stellar local elementary school system in their part of the city has led to some educational deficiencies that require intensive remediation in the high school.  The lower test scores and metal detectors in the high school make an otherwise beautiful suburb look like a dodgy place to live.

I hate to say it but the metal detectors have made a difference in the high school here.  Does the recent incident in Murraysville mean the entire suburb is dangerous?  No, but let’s face it, teenagers are special creatures.  Their brains are undergoing radical changes and they can careen out of control in a nanosecond.  Short of putting them in a state of suspended animation until they’re 21, maybe we should bring out more metal detectors in the middle and high schools.  That doesn’t violate my free range philosophy very much.  I still object to the silly expulsions and suspensions for playacting and bringing butter knives in packed lunches.  But stopping an idea at the door and giving hot headed students a cooling off period?  I think I can live with that.

It could happen anywhere. My district feels a teensy bit safer than Murrysville today.