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      I don’t know.  But Pinochet did the same (plus rats), it’s not without precedent. I hope not: The war veteran, who loathed manipulating Western politicians even as he defended tactics of collective punishment, continued his account: Afghan prisoners were tied face down on small chairs, Jack said. Then fighting dogs entered the torture chamber. “If [...] […]
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The problems with mergers

No nuts for you.

Tim Wu at the New Yorker wrote a piece about the all too predictable outcomes when United merged with Continental back in 2010.  There were sharp increases in fares in newly uncompetitive markets and a gradual decline in overall service.  I think the decline goes back even farther than that when United eliminated or sharply reduced pensions for flight crews and pilots back in the early naughties.  I remember distinctly the beaten down and depressed looks of the flight attendants on one of the flights I took from Philadelphia to Denver when I was on my way to a conference. When asked, the flight attendant made some remark to the effect that she had lost a lot in retirement benefits. It felt like we were hurtling towards Soviet era customer satisfaction with poorly compensated and indifferent flight attendants. Was this really what United wanted its customers to experience: a demoralized employee workforce, fewer services and a plethora of new fees, the profits from which were not going to the employee pension fund?

By the way, Tim, that ritualized abuse that you feel Americans are experiencing after the approved mergers of airlines and cable companies, for example?  I call it “exploitative profit mining”.

Then I saw that the New York Times Magazine was doing a big story on the lack of productivity in drug discovery (which I have been predicting for years now) and maybe it was time to go back to “trial and error”.  Now, I’m not going to say they’re wrong because we have tried proteomics, genomics, combinatorials, target based drug design, RNA interference and a whole lotta other “omics” type technologies and none of them have pulled off the “immaculate reception” to save the game that they promised to deliver.

But the thing that really made me laugh was the idea that any bean counter is going to let the R&D division go back to “trial and error”. My last impressions of the industry just before Pharmageddon was that “trials and errors” were distinctly money wasting activities. First, there was no metric that could be applied that could accurately determine exactly how many trials would be necessary to achieve the desired outcome. Secondly, there was the negative word “error”. Error implies failure, not a measurable objective, like a lead in the pipeline. To MBAs and the finance industry that now direct drug discovery research, it is important to minimize negative outcomes like errors, nevermind that it is the way the scientific method works and that we learn as much from error as success. Errors are the way we eliminate dead ends and turn our attention to more promising avenues. It’s how we work the kinks out of all those “-omics” technologies. Whatever. Executives would much prefer “predict and succeed”, which is theoretically a better use of time and money but rather less like science.

We might also try to eliminate the mergers and acquisitions of the drug companies by bigger drug companies, a trend that has interrupted project after project in the last two decades and caused the elimination of entire therapeutic areas. The increase in mergers occurred at the same time that biology is undergoing a 21st century scientific revolution. The finance industry’s unchecked enthusiasm for trading drug companies like baseball cards has blighted many promising new technologies and the careers of thousands of highly trained scientists, hence, no new blockbuster drugs. We probably do not need to conduct any additional trials and errors in merger experiments before we kill off the field entirely.

Just my non-MBA opinion but the lack of blockbuster drugs in the pipeline was entirely predictable fifteen years ago by those of us who experienced the joys of constant M&As. Maybe the bigger problem is that the MBAs never asked those of us in the trenches about the effect of mergers on productivity. Hmmm, one can only imagine why…

Derek Lowe and his insider commenters weigh in on the New York Times Magazine as well.

Hacks and thwaks

Yesterday, for some bizarre, unknown reason known only to Yves Smith, I was accused of spouting PR for the pharmaceutical industry.  It appears that it goes against left of center dogma to say that the NIH does not just hand over perfect drug entities to the drug industry, already tested and bioavailable and efficacious, and that all the industry “R&D” divisions (well, what’s left of them) do is add a few finishing touches and charge everyone an arm and a leg for them.  Yes, that is what pharmas do.  They don’t really do research.  We just accept these gifts of government largess and when they arrive on our front door steps all glistening with ingenuity and brilliance, we stand around and marvel at them like they are alien creations.

Ok, the chemists can stop laughing now.  No, really, you’re going to hurt yourselves.

The truth is that NIH grants allow for some good science and many new discoveries.  But very rarely do they get to the stage where a new drug is delivered to a pharmaceutical company as a fully formed entity that requires no modification.  My experience (>20 years in the industry) is that NIH grants fund a lot of basic science on targets.  Then, if those targets (not drugs, protein targets) look interesting, they’re picked up by a pharmaceutical R&D, or more likely, several pharmaceutical R&Ds because the information is public, and all those different companies work on the target at the same time.  That’s how you get “me too” drugs. Just because someone beat you to market doesn’t mean you can trash all your hard work. Besides, your drug might actually be better.  It is strange that it is only in the pharmaceutical industry that “new and improved” is looked on as a bad thing.

Now, I am not going to argue that the pharmaceutical industry doesn’t charge an outrageous amount of money for new drugs these days.  And I won’t argue that they haven’t done much of anything to put new drugs on the market.  Or that they haven’t gone back into their old compound libraries  or that they reformulate things.  Sometimes, those reformulations are meaningful and sometimes they are not.

But I do know that research is expensive.  Ridiculously expensive.  That’s why big pharma has been cutting back on research as a counterintuitive business model.  That’s why there’s nothing coming out of the labs.  They are spending less money these days and they are relying on academic groups more often now.  The reasons are many but chief among them is that after having spent many billions of dollars on research, very few new drugs were approved by the FDA.  And that could be a result of higher safety standards that didn’t exist when the project was started or the constant mergers and acquisitions and bad management and the explosion in biology in the past couple of decades and the new and trendy things that snake oil salesmen corporate ladder climbers sold to their bosses as the next big thing that weren’t ready for prime time.  In fact, if Yves had been reading the posts I have written in the past several years on the pharmaceutical industry, or Derek Lowe at In the Pipeline has been writing (check the archives, Yves) or even someone like Anthony Nicholls at Openeye has been writing, she would have gotten a more complete picture of what is really going on.

What is really going on is that the big pharmas are going “weightless”.  They think they can exploit little start up companies and academic groups and turn those compounds into drugs.  And they want a cheap workforce.  I mean REALLY cheap.  Like $37K/year is their ideal top of the salary band for post docs who will never find a job in industry.  So they have been pushing this nonsense to the White House and Congress that what we need is more students who will sacrifice themselves to STEM professions and forget about having a stable job or family life because it is the patriotic thing to do.

Meanwhile, there really are academic groups that are trying to create new drugs.  They consist of former industry professionals who have taken incredibly steep cuts in their salaries and work in facilities where their resources are vastly reduced compared to their formerly corporate lab environments.  The pharma industry has them right where they want them, using their decades of expertise to cobble together drugs out of shoestrings and bubblegum.  And those dedicated scientists spend a lot of time applying for grants from the NIH but the money is very hard to come by and can’t pay for all the things and people they need to do their jobs.  These people are amazing and I can’t say enough good things about them.

But they are the exceptions, not the rules.  The rule is that the vast majority of NIH funded research provides germs of ideas.  They are hints of possibilities, a bunch of gel slides and some correlations.  I have been on many projects that started with a few interesting papers from NIH funded research.  We spend a lot of time on these shiny little nuggets setting up assays and crystallizing proteins and screening millions of compounds and synthesizing new compounds only to find out that the NIH funded studies did NOT have all of the answers.  The initial studies had only part of the answers and didn’t know about all of the other pathways and upregulation or the initial study was just off and the assays don’t work like they should and the project has to solve a different problem before it circles back to the original problem.  In the process, the industry research uncovered many aspects of the biology that the NIH scientists didn’t have the time, money or urgency to discover by themselves.  Many millions of dollars have been spent chasing NIH beginnings that ran into brick walls and had to be abandoned.  In any pharmaceutical company, there were dozens and dozens of these kinds of projects going on all at the same time.  Many projects are started but bloody few succeed and the vast majority of drugs that are produced from the germ of an idea that came out of an NIH study originated in the compound library of the pharmaceutical company itself.

Those are just the facts, Yves.  You can talk to anybody who has ever worked in pharma in the past 20 years and they will confirm this.  Yes, some remarkable things have come out of academia but very few of them  came directly from some academic lab untouched.  All of the other drugs were industry generated.

The reason why drugs are so expensive and are going to get more expensive is because more companies are abandoning their small molecule drug discovery efforts, because they couldn’t get approvals and recoup their investments before the patent clock expired, and are now moving into biologicals, the next big thing.  Oh sure, there will be some small molecule efforts in areas like oncology but this is due to a very cynical calculation on the part of the bean counters.  Oncology drugs are fast tracked and the safety profile is relaxed. People with death sentences on their heads are more than willing to become human guinea pigs and put up with a lot more toxicity than average non-sick people. They’re less picky about formulations.  Sure it would be great if the drug is oral and easily bioavailable but if you have to take it by IV, that’s OK too. If the drug extends life by even a few months, some families would consider that a success and they’d be willing to pay whatever the market wants.  And best of all, patients don’t complain and file class action lawsuits.  If the treatment succeeds, everyone is happy no matter how much the liver is shot.  If it fails, well, the patient was going to die anyway.  The relatives chalk it up to fate. The shareholders are happy.

Biologicals are a whole different animal with their own share of problems from humanizing mouse antibodies and aggregation problems to all kinds of new and different things that no one even knew about the cell.  It’s going to be interesting and very expensive.

The rest of the non-wealthy people will have to live with generics, which are bound to get more expensive.  Yves is smart enough to figure out why because she understands scarcity, supply and demand.  But these will be older, less efficacious drugs.  Well, the public put it’s foot down about “me too” and demanded a higher level of perfection than any small molecule drug is likely to ever deliver and this is what happens.  No more new small molecule drugs.

There are many facets to this problem.  Everyone sees the issue they are closest to.  If you only consult one “expert”, you only see one part of the problem.  There is no reason to distrust those of us former industry professionals who have a different version of events.  Believe me, we are not going to tell you a lot of flattering things about the pharmaceutical industry that stupidly laid off all of its expertise.  But unless you find out what is really going on and who is doing what with which resources and how successful those resources are, you can’t develop a complete picture of the landscape of this problem.  And more importantly, you can’t *solve* the problem. That smacks of a very unscientific approach to solving problems and, in the end, it doesn’t serve the patients or American citizens well at all.  In fact, not gathering as much information as you can from different sources is precisely what Big Pharma wants you to do.  It’s asymmetrical information at its best.  You only have one part of the picture and they just sit back and laugh at your righteous indignation while you rail against them.  How is this different from the finance industry?

By the way, I am no finance person and I didn’t much care for economics.  But I took the time to read books and ethnographies and visited wonky sites and read Yves and waded through all this money crap that interests me not even in the slightest.  And although I don’t know everything, I know much more than I did four years ago.  I know what motivates the bastards now and what incentives need to be changed to make the system function again.  That’s a positive step, right?

So, maybe closing your ears to differing points of view is not a good thing, Yves.  You’re not helping us beat this thing.  And that is something no pharma PR rep would ever say.

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

And now for some IKEA hacks!

This first one is from one of my new favorite YouTubers, goodbrowngravy, who despite being a white southern male with an accent, appears to be not the ignorant redneck that some lefties think all white southern men are.  (Do we condescend and stereotype much?  I think we do.)

Here’s goodbrowngravy’s IKEA hack of a Rast dresser into a campaign style side table.  Nice work!

And here is a hack of an Expedit unit turned into a stereo system from Apartmenttherapy.

Speaking of IKEA, if you are in the area tomorrow of the Elizabeth, NJ IKEA, you can drop off some badly needed items for the NYC/NJ survivors of Hurricane Sandy. IKEA is teaming up with the RedCross and other organizations to provide furniture and funds and also to collect items from customers who are shopping on Sunday. Check here for a list of items that would be much appreciated.  The collection will start at 11:00am.  And I really need a Rast…

A Pleasure in Work

The late John Huston once said, “Choose your career as you would choose your spouse- for love and money.”

The money part has been dogging us for a couple of decades.  We’re so worried all of the time over whether we can pay the bills that we tend to forget about the love of work.  Your job is a place where you spend 1/3 or more of your day.  You should enjoy it, look forward to going to work in the morning, be excited about solving new problems, deliver service to your customers to make their lives a little better, put quality into craftsmanship.

I consider myself very lucky to have a job I love.  Recently, it has gotten much more interesting and I look forward to going to work each day to collaborate.  This is a serendipitous revelation for me and makes me realize that learning new things can keep your mind flexible and young. For people like me who have wanted to do science since they were children, to have a place to go to discover the wonder and delight of nature is a thing divinely to be thankful for.

So, I was deeply saddened to see the following labor statistics:

Pharma Layoffs per Month, 2010

Month Layoffs
January 8,170
February 17,687
March 308
April 1,049
May 6,943
June 830
July 2,023
August 255
September 6,069
TOTAL 43,334

Even more disturbing is what the layoff picture in R&D looks like over the past two years:

Industry 2010 2009
Government/Non-Profit 123,469 109,433
Pharmaceutical 43,334 52,683
Retail 31,246 88,352
Computer 22,609 61,578
Telecommunications 22,609 53,145

Source: Challenger, Gray and Christmas

Regardless of how you may feel about Big Pharma, the loss of almost 100,000 jobs in the past year should set off alarm bells.  Although a number of the layoffs have been related to reduction in pharmaceutical sales staff, an increasing number have been to scientific staff, specifically medicinal chemists, whose jobs are going to China and India, possibly permanently.   Other layoffs in R&D are a consequence of mergers and acquisitions where salaries of scientists, frequently located in very high cost of living states, are considered a drag on the bottom line at a time when patents are expiring and new drugs can’t be approved by the FDA.

That’s thousands of well trained, dedicated scientists whose knowledge base is gone from the American workplace landscape.  It is destruction of American scientific infrastructure on an unprecedented scale.  But more than that, it is the loss of eager minds with almost childlike enthusiasm for science that will doom us as the greatest nation on earth.  In order to keep discovering new breakthroughs in physics, biology, chemistry and medicine, we need a place to go and the means to keep a roof over our heads.  Even scientists have base level caloric requirements and families and children.

I hope that lawmakers  and businessmen wake up before it’s too late.  There’s more to life than making obscene gobs of money.

To close out this post, here’s a video of crystallographers from the University of Michigan riding tricycles around the Advance Photon Source Syncrotron at the Argonne National Labs.  May we all stay forever young, as learners, employees and American citizens.

Thursday Morning News and Note to the DSCC

The last time I saw Paris...

The last time I saw Paris...

Before we get to the cafe au lait and croissants, I’d like to relate an encounter with the remnants of what *used* to be my party.  A few days ago, the Democratic Senate Campaign Committee, the DSCC, called me at home to hit me up for a donation.  Almost immediately, I told them to save their breath.  I had no intention of contributing money to any arm of the Democratic party after what transpired during the primaries last year.  I told the phone guy (and it’s ALWAYS a guy) that I had left the party over the primary debacle.  He sounded confused, like a boyfriend who can’t possibly understand why you are mad at him for acting like a jerk.  He asked me to explain so he could pass the information on.  So, I told him: I voted for Hillary in the NJ primary, a primary she won by more than 10 points, and watched every one of our delegates go to Obama during the convention.  Does my vote count or not?  If it doesn’t count, then why does the party expect me to give it money?  I’m not stupid.

The guy laughed at me.  It was a laugh of both nervousness and contempt.  Contempt, I suspect, because old, uneducated, working class, sino-peruvian lesbians aren’t supposed to really count even when they are not old, not uneducated, and are professional straight, scientific researcher women such as myself.  If you’re not twenty three and impressionable, I guess you might as well apologize for living and forcing people to gaze upon your aging visage.  Your intellect is of no interest to the guys of the Democratic party.

The nervousness was new.  Yep, the guy tried to pull off a mocking laugh, the kind you reserve for losers, but there was something behind that mockery that belied the confidence.  I don’t know how many women had turned this guy down on the phone but maybe I was the first that gave him an actual reason that made sense.  It must suck to find out that you’re no longer the guy you thought you were and women are on to your lies and your secret viagra stash.

Get a clue, guys.  You took our votes and forced Obama down our throats in your primary rape fantasy and we’re not ever going to forget it.  He turned out to be exactly what we said he was: an overly ambitious, shmoozing, political opportunist without a political philosophy, experience and hard earned relationships necessary to get things done.  There’s no 11 dimensional chess going on here.  Just a bunch of jerks who thought they could write off the votes of millions of people, many of them women, and get away with it.  Go ahead and laugh.  You’ll never get a penny from me.  And you may never get my vote again.  You don’t have to be a crazy nutcase birther to know the devils by the look in  their eyes.

Now, onto the news:

Slate’s The Big Money is behind the curve when it comes to Sheila Bair.  I believe we covered this months ago.  (In January, and  July, not to mention Dakinkat‘s stuff from two days ago) But, hey, it’s nice to see other media types are getting with the program and realizing that sexism costs.

The NYTimes reports White House Affirms Deal on Drug Prices.  I’m not sure what that means ultimately.  As I have pointed out before, the pharmaceutical industry has some very legitimate reasons for wanting to work with Congress and the WH on issues concerning the drug industry and health reform.  But it’s really cutting its throat going with a lobbyist like Billy Tauzin and jumping in with the health insurance industry’s public relations team.  Big Pharma’s concerns are not the same as the health insurance company’s concerns.  We actually produce something of value, remember guys?  Ah, Jeez, there are those *guys* again the ones who run the drug industry.  The clueless ones who still think that the most important activities in a pharma company happen in marketing, advertising and acquisitions instead of the lab.  Just forget it.  Lay us all off now and get with dismantling the US research community and moving it overseas.  Just get it over with already.

Jon Corzine is still behind and Christie’s lead seems to be widening. Cue the schadenfreude. {{snicker}}  Corzine’s campaign is planning to launch a spot featuring Pres Barack Obama himself when he came to NJ to rally for the governor.  Polls indicate Obama’s appearance mattered not a whit.  But this little bit from Obama on Corzine’s accomplishments had me laughing:

“Jon Corzine has not only protected funding for New Jersey schools, he reformed them with tougher standards and now students in New Jersey rank at the top of the country in reading and math because of Jon Corzine.”

Yes, indeedy. If your kid is an average to bright learner in NJ, or if you have a special needs kid, NJ public schools are pretty good. Not the best with clear, concise, non fuzzy standards that over romanticize the child. But not bad.
However, if you have a kid who is very gifted, you enter into a Kafkaesque nightmare of educational ideology exacerbated by almost complete lack of funding from state and local governments. How much non-funding of the state’s gifted and talented program is unclear at this time. There is no information on whether there was any funding for these underserved students for 2009 but recent years indicate that these programs in the state of NJ got zip, zilch, nada. There are also virtually no standards or mandates regarding their education, leaving them at the mercy of teachers who have never been trained in the care and feeding of gifted youth.

Yep, here in NJ, the home of Einstein and Edison, the birthplace of telecom, the home to research laboratories that crank out cures for cancer and schizophrenia, the gifted and talented students are treated as inconveniences. As the mother of one of these kids, who absolutely hates school here, I can attest to the whack-a-mole approach to getting her educated at her developmental level. I and many of my colleagues have had to scramble to meet our gifted kids’ educational needs through a series of summer courses at local prep schools, distance learning through programs for gifted youth at Stanford University and by homeschooling. That’s what my outrageous property taxes in NJ buy me in NJ- a school system and education department that is completely unresponsive to the needs of my kid. And Corzine during his tenure, has done less to improve this situation than many states in the south to service this population of students who could potentially solve the energy crisis, invent a new cure for cancer or be our next political leader. Your gifted kid gets better treatment in Texas and Georgia than in NJ. NJ ranks right down there with Alabama.

Gifted by State

Gifted by State

Thanks for nothing, Jon. It’s just one more reason to skip the election this year.

Well, that and the clueless idiots of the Democratic party.

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