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Friday: Anthony Nicholls amazing rant

Will the last one out please turn off the lights?

Today is my “Release from Wage Slavery!” day.  There’s a bottle of bubbly in the fridge left over from New Year’s.  I’ve debated whether to drink it now or wait until I land another job.  The most ironic thing about being laid off for me was that I got so busy after it happened.  In fact, I didn’t get it all done.  There’s a structure that needed a few more steps of refinement and at least a day of tweaking.  Nah-gah-happen.  Then there’s that threonine that’s taunting me.  Arggghhh, it kills me to leave it all hanging like this just when I thought I was onto something.

Last night, I followed a link from Derek Lowe’s blog, In the Pipeline, to a cathartic post from Anthony Nicholls who runs OpenEye.  Here comes some geek speak:  I’m a big fan of OpenEye.  They make an application called ROCS that allows for shape based searching of chemical structures in 3D databases.  I’d put ROCS right up there with SMILES in terms of computational chemistry innovations.  Once you’ve gotten the hang of it, it’s hard to see how you can live without it.  It’s versatile like an iPad.  There’s no one way to use it.  The variations are endless.  This was brought home to me yesterday as I was closing out my notebooks (yes, I’m one of the few modelers who even keep the damn things).  I was indexing the entries and couldn’t help but notice how many times I had used ROCS, OMEGA and most recently, BROOD.  Excellent tools.  I’m really going to miss using them.  Next to some more bloated software suites, OpenEye is cheap.  A great bang for the buck.  But I can’t afford even a single user license on a severance package budget. (There might be a business opportunity for Anthony in that for the newly independent modelers who need to keep their skills fresh until they land their next gig.  hint, hint)  Ok, enough of that geeky stuff.

Anyway, back to Anthony’s rant, What’s Really Killing Pharma, I think Nicholls nails it- almost.  There is something he left out that puts the whole demise of pharma into perspective.  (For those readers out there who are lifelong enemies of pharma for ideological reasons, please don’t get in a snooty snit over it or you will be missing the point of Nicholls’ post.  This problem goes beyond the misperceptions about “me too” drugs and outrageous pricing.)  The whole post is worth a read but some parts stand out for special attention.  It’s almost as if Nicholls has been spying on us (it’s funny how he can’t resist adding references even in a blog rant):

But what has actually happened? First, a lot of senior scientific talent has moved on—some through retirement, others preferring to work at smaller companies with less of the “world-class management” big pharma can provide. But what has shocked and distressed me is the number of people in their fifties who have been let go. These are the people who actually have a working knowledge of the fifty years of pharma Witty mentioned, people who have done their “10,000 hours” [2] refining unique and irreplaceable skill sets, people who can pass these skills on to others. If you accept that making drugs is more art than process, then these are the last people you let go.

But even this travesty pales next to my next point: the danger of management fads. Because your modern big pharma CEO knows next to nothing about science, I have to assume they think they are adding value by imposing management schemes they do know about. Let’s consider one such disaster of a fad: lean thinking and six sigma. Originally developed at Motorola by Bill Smith but based on earlier concepts from Genichi Taguchi and others, the concept is simple enough: apply statistical modeling to an industrial process so that one can gradually improve that process. Actually, this principle is not dissimilar to my decrial of the lack of statistics in molecular modeling—if you don’t know where you, are you never know if you have improved. The problem, though, is the process being modeled here—drug discovery—doesn’t lend itself to this method. As any senior medicinal chemist or molecular modeler would be happy to explain to management, an embarrassingly large fraction of drug discovery involves serendipity—while you’re looking for one thing, you find another. And serendipity is, of course, the complete antithesis of a Taguchi robust process [3] where variance, i.e. a standard deviation, can well defined- we work in the domain of the unexpected, the domain of the “Black Swan” [4]. Now that the method has been applied and failed, it seems ridiculous to have ever thought it might have succeeded. But not only was it applied with great vigor, it often came to be seen as a much more secure employment path than the vagaries of drug discovery. Not a little talent was wasted on these meaningless exercises and not a few careers lost to management bullshit.

Another good one: empowering IT departments to make scientists use the same infrastructure as the guy at the front desk. Rather than see that scientists often have different computing needs than other parts of the business, IT demands obeisance to the corporate norm. In doing so, they hinder the kind of innovation (e.g., Linux, GPU solutions) that used to regularly occur because scientists are quite computer literate, thank you. Instead, IT departments make it impossible for competent people to manage their own resources. They create obstacles instead of removing them. Machine was made for Man, not Man for the Machine.

More fads? How about metrics and cross-charges? In this Through-the-Looking-Glass world, scientists have to account for everything they do, with the cost of each and every action weighed and accounted for. Work done by other groups is counted as “services” that have to be expensed. In other words, upper pharma management—convinced, perhaps, that scientists don’t know the real-world cost of operations—are ruining the one indisputable advantage of a big company: the fact that you can just walk down the corridor and get the another person’s expertise to help solve a problem. They are building walls that turn a large company into a thousand little independent entities with all the problems of communication and lack of shared vision that implies. That’s the newest, most amazingly dumb-headed, most disastrous strategy. Now tell me, does this empower your researchers? Does this “remove obstacles”?

That was orgasmic.  I need a cigarette.

I have *been* there, especially with respect to fighting the corporate IT department.  How much money and wasted time has been spent hiring contractors, who don’t have the security clearance to get the sys admin password, to manage our linux workstations and clusters to corporate IT standards.  I can remember when I first started my current gig when we were transitioning from IRIX to RedHat and I had to deal with some pretty clueless borgs in IT purchasing who weren’t going to let me order the new workstations for our group because the only computers we had a contract to purchase had to have Windows on them.  We finally got the workstations and had to have Windows removed, which violated a warranty.  It was ridiculous.  So much time and email spent trying to get the IT department to understand why we needed a different operating system.  If pharma wants to save money, they will get rid of the bulk of their useless, paper pushing, “we only do one thing”, IT bureaucrats and give in silico sciences the things they desperately need- their own sys admins and private networks separated from the rest of the accountants and salespeople.  And for God’s sakes, get rid of IE6.  No one uses it anymore.  Please don’t tell me you’re only interested in security when you shut down my Chrome browser and then force me to do BLAST searches on IE6.  No amount of fencing the campus and card swipe enabled portals are going to keep determined bad guys out of your databases if you can’t keep up with the latest security features of your old Windows operating system.

And don’t even get me started with the charge backs to other departments scheme.  It’s stupid beyond belief for research.  And here’s why: research happens by trial and error.  Sometimes many trials and errors. (Actually, I’m encouraged that statistics and  “design of experiments” is starting to catch on in protein engineering and expression but even using “design of experiments” is going to take trial and error.  There’s no getting around it.)  Yes, it can be expensive but if you have to limit your trials because a.) your budget has been unrealistically reduced or constrained and b.) negotiating every transaction takes away from your time at the bench, then you have effectively strangled the baby before it has a chance to grow.  I’ve already seen this in action.  Project teams want and need your expertise but the company is forcing them to pay for it out of a vastly reduced budget and they have to weigh every choice very carefully.  What happens next?  The project team is either forced to forgo this vital knowledge or pay an outside company to do it.  But an outside company is constrained by science as well.  THEY need to go through a process of trial and error too in order to deliver what the project team has ordered.  And that means the project team will get a limited number of attempts to get the information they need because otherwise, the outside company is going to start charging them for everything that goes out of the scope of the negotiated contract.  AND, here’s the real kicker, the outside company can sell that protocol to some other company.  If your project team wants to keep the information exclusively, there is an additional charge.  How is this cheaper than going down the hallway to ask if the hard working little department (that is getting laid off) if they can do it for you?

BUT, there is one aspect of this problem that Nicholls has missed (or maybe it’s in his next missive on the subject).  The problems that Nicholls has illustrated are not unique to pharma.  Maybe they have a disproportionate effect on pharma because some parts of the process are more sensitive to external pressures.  But in general, the effects of mismanagement by the MBA Bonus Culture can be seen in every industry from banking and finance to automobiles and chip manufacturers to television and cable media companies.

Here’s my theory about how it all went south since the 90’s: It’s the 401K.  Yep.  It puts the whole dismal phenomenon in the proper framework.  But how could something that appears to be so innocuous bring the country’s scientific and industrial framework to a screeching halt, you ask?  Think about it.  MBAs and executives are hired by corporations to “increase shareholder value”.  Before the rise of the 401K, that meant building a better mousetrap and finding a better aspirin.  Now, the only thing that matters is pleasing the finance guys who rate your stock from buy to hold to sell.  And those same finance guys have a stake in the outcome.  They set their own terms of compensation as well as service large institutional investors and mutual funds that we get to choose from in our 401K plans.  Corporations are now driven to serve the finance industry and the shareholders, which are us.  They’re not in it for the new products anymore.  And once you start hiring executives whose goal it is to optimize the ROI, well, it doesn’t matter where the money comes from anymore.  It’s just money, numbers on a spreadsheet.  It doesn’t matter if those numbers represent people with families and caloric intake requirements and 10,000 hours of expertise.  It doesn’t matter if there are fewer products to sell.  Once the patent is dead and the money is gone, the investors will follow the money to the next hot thing.  There’s nothing mysterious about this.  It’s not personal.  It’s just the reward system we have set in place since pensions became too old-fashioned for those up and coming 30 somethings in the 90’s (um, that would be us).  We’re like rats pushing a pellet bar for another shot of cocaine.  We can’t help ourselves and will keep doing it until we die from the pure pleasure of getting that next teeny bump to our retirement accounts.

Now, is the 401K the only reason why pharma and other industries in the world are starting to topple and fall like Ozymandius?  No, of course not.  There are other forces at work here, like the FDA that really needs to get its act together and out of control lawsuits that are affecting everything from pulling pretty safe drugs off the market but leaving stuff like Tylenol available for anyone to buy off the supermarket shelf to potentially destroy a liver or two to making it impossible for school age kids to have a normal life of scabby bruised knees after a vigorous afternoon at the playground.  We lefties are partially to blame for the overly litigious nature of American culture where everyone has an opportunity to plunge their hands into the deep pockets of someone else’s bank account or insurance policy for the slightest of injuries.  How many of us realize that the money guys just pass the costs onto the consumer and keep on partying?

But I have run out of time this morning.  I have to go to work, for the last time in what may be a very long time, and finish transferring my files.  Then, I will drop my keys, SecureID, credit cards, dosimeter and employee badge into an envelope and say good-bye to the best job I ever had.

36 Responses

  1. Here’s a “big pharma” experiment. Look at the top selling drugs. Nearly every single one of them is for a “disease of civilization” rarely seen in hunter-gatherer societies. The only ones I would consider real, honest medicine are the opiates, and even those are mostly adulterated with toxic Tylenol because the state says it’s better for you to be dead than high.

    USDA and FDA continue to promote bad science to prop up their dying reputations, and to protect the corporate overlords who just love it when the state tells the sheeple that the competition’s products are unhealthy. Of course the “competition” consists of all that food we were eating for millions of years before these marketing geniuses came along, or even before agriculture. How did we ever survive before heart healthy whole grains and heart healthy processed industrial seed oils (a better term for so-called “vegetable” oil)? Oh you silly, they say, cavemen died young — don’t you know all that saturated fat will kill you? Yes, the same palmitic acid that courses through your bloodstream when you don’t eat, nature has designed to be poisonous! So don’t eat meat, the food that made us human — eat what made us slaves, what makes us fat, what makes us sick — and pop lots of pills, and don’t be alarmed when you hit 40 and feel twice your age. We’ll hook you up with all the statins you could hope for, and who cares that no credible study shows any benefit from them, and even shows increased risk?

    Drug pushers of all kinds — legal and “prohibited” — depend on the state to prop up their industry and provide them with the profits they enjoy.

    • That business of sticking Tylenol in drugs where it has no purpose is disgusting!!! Most people have NO IDEA how dangerous Tylenol is — I’ve had people argue that it wouldn’t be sold over the counter if it was so dangerous — that it’s safer than aspirin!! OMG … It’s really amazing that it hasn’t killed more people.

      • I really like reading stories about life right after the discovery & development of penicillin. It’s power was almost magical.

        I myself was affected by it. I had an ear injury & the docs told my parents I’d probably be deaf in that ear. But, they tried using that new-ish drug …. I got penicillin shots everyday for two weeks and my ear healed perfectly.

        It’s amazing what a few years & genius-luck can do.

    • Did you read my admonition about sticking to ideology when reading this post?? You have completely missed the point.
      The point of what nicholls and I have been saying for some time now is that research is dying. It us being killed off by business types who don’t understand research. And it’s not just here in America where this is happening. It’s global.
      Hey, if you don’t like the drugs we make and you want some pure hunter gatherer lifestyle where the average lifespan was something like 30, if you managed to survive childhood, more power to you. No one is forcing you to put anything impure in your body, the Temple. But you don’t have to bore me with your anti-science screeds. Why don’t you go hunt for dinner?

      • Color me actually slightly surprised that even though I scoffed at the absurdity of using “average age”, that was one of the first straw men you went for.

        • Sorry about that. But if you had a been reading this blog for awhile, you would have known that I have very little patience for members of my own tribe who pop off uninformed opinions about how they *think* pharma works based in years of crazy assed $#|^ from class action lawyers and crunchy granola types. It you don’t like the products, don’t take them. But don’t YOU who has never worked in pharma presume to tell ME who has worked my entire career there, what our motivations are and what those drugs actually do. Because you just end up sounding deluded and clueless to me.

      • To call this attitude “anti-science” is to miss the fundamental points on a truly astounding level.

        • Hey, you were the one who said statins didn’t work when I know plenty of people who inherited their high cholesterol problems who are being kept out of the cardiac unit by them. I suppose you’re going to tell me my mother’s high blood pressure problem is not *really* being controlled by her ace inhibitor. Or that my dad’s cancer wasn’t being held in check by the taxol analog. Or that the adult booster DPT shot I got last week is going to make me autistic. Please spare me. Your beliefs are about as unscientific as a creationist’s. Lefties who are determined to stick to their beliefs in spite of overwhelming evidence to the contrary are in danger of looking as ridiculous and untutored in science as the fundies they mock on a regular basis. You can’t discuss real problems in pharma or nuclear energy or genetically modified “name your crop du jour” with them because their ideologies get in the way of their ability to learn and process new information and put it in its proper perspective.
          Don’t waste my time with this nonsense.

  2. 😦 I’m so sorry, Riverdaughter.

    That article sounds like something you’ve written — I’m off to read it now.

  3. I’m sorry to hear about your job loss. Your critique of the soul-killing zombie corporate culture that has been imposed on every intellectual or creative endeavor in this culture is right on. And as you point out, it doesn’t just change the business model, it ultimately kills the creative work itself. But the loss of scientific spark and initiative is among the greatest casualties, and we lose one of the signatures of an advanced civilization.

  4. A totally non-ironic “good luck!”

    My experience on leaving the cube is that my life is much much more interesting and fun now than it was then. Financially, it’s been terrible, but I’m still much better off than some, and “retirement” is a dram, but I never wanted to play shuffleboard anyhow.

    So there can be positive outcomes from a change like this, and I hope the best that can happen does happen.

  5. Thanks for the kind comments- I’m glad you liked the rant and for your additional insights. On the matter of getting a license after your severance, that’s easy. If you want to use the tools for non-commercial purposes they are free, and even if you want to do consulting with then we can normally work out something practical. I made the company to make products that get used; glad that you got to use then and hope that continues.


    p.s. the “Branded” clip was genius!

    • Thanks, ant. I still have your presentation from the openeye user group meeting a few years ago. Not your typical dry presentation. 😉 I think it was something like, “forget everything I ever said about electrostatics before. I just realized we don’t know all of the physics we need to know and we’re all talking out our asses. I have to redo everything.”
      Very refreshing.

  6. Michael Lind did a post recently about this phenomenon, about how we went from a business culture that was about making a better mousetrap to maximizing “shareholder value” whether that made sense in the long run or not. Ian Welsh did something similar, too, and I’ve attached the links below if anyone’s interested. Hopefully more and more of us will start to realize what you’re pointing out!



  7. I just had to weigh in on the “evil Pharma” rant. I have big problems with Big Pharma and it’s political shenanigans. But I have nothing but love for researchers like you. I have a rare cardiovascular disease (that is NOT acquired, thank you very much) and would be dead now if it weren’t for the miracles of calcium channel and beta blockers. Even a few decades ago, I would’ve died. So, THANK YOU! I hope you find a place to go back to doing what you love soon.

    • Corporate culture can be soul crushing but I was very fortunate to work for a group that made my work so much fun that I actually loved going in. In fairness to the group managers, they had no part in the decision to lay me off.
      One other thing I think is being missed by lecture is that research in a corporate setting can be very efficient. You can achieve an economy of scale that consultants and small biotechs can’t. It also makes it much easier to collaborate and get the services you need from other groups with expertise that is different from yours. I have no regrets about working for a large corporation. Sooner or later, management will get the boot. The situation as it is is unsustainable.

  8. Beautiful rant, RD – and right on the mark in so many ways. I particularly enjoyed the management fad discussion. Two jobs ago (heh!) the national lab I worked at (which shall remain nameless) was turned inside-out by precisely this sort of nonsense. Groups that had formerly collaborated freely were placed into thoroughly stovepiped divisions that never spoke to each other. The reorganization required adding an entire layer of new management and supporting staff – which caused the layoff of a sizable number of scientific and technical staff in order to free up the salary dollars to pay for them. It was crazy.

    Good luck in your search (which you should have started a month or two ago but didn’t).

    • {{snort!}}. I spent the last two months making a s}%^load of structures with BROOD from some of my own proposed structures. Couldn’t help myself. Both of my projects are high profile so I have to wait until they’re cleared by legal before I can add them to my CV.
      It’s not like I haven’t been sending out my CV. I have. It’s just that I want out of the northeast and, unfortunately, Cambridge is where the jobs are.

  9. […] The Obama workers’ paradise is coming. More and more will soon be liberated from the constraints of work. […]

  10. “Another good one: empowering IT departments to make scientists use the same infrastructure as the guy at the front desk. Rather than see that scientists often have different computing needs than other parts of the business, IT demands obeisance to the corporate norm.”

    Years ago I wrote a text book about data processing. I had one segment which talked about the “Priests In The Temple” style of 50’s era computing and the gross manipulation of upper management by the mysterious computer priests. The era of the personal computer ended that –for a while. But then, predictably, the priests found another way to block the temple portals– the Internet. Now the priests use internet compatibility and viruses to achieve the same end. The users are stuck with this bottle neck until the Matrix arrives, when once again, we can all be priests.

    • Well, part of the problem is that most corporate IT types are pretty much ignorant about scientific computing.

      • Went to a presentation at peptalk in San Diego in January on cloud computing. It would be great for those megauber virtual screens that need to be done once in a while. Why have a dedicated cluster sitting idle for a good portion of its useable life, right? So the dude said, amazon can do cloud services pretty well with a higher degree of security expertise than your typical scientific computing and global IS department. The R&D level lawyers signed off on the proposal and proclaimed it good to go at one company. But it got stopped at the corporate global legal level. Why? Because the global corporate lawyers had only had to deal with windows enterprise level contracts. Microsoft the know. This cloud stuff? Completely new territory. Needs new security policies, protocols, different contracts and a whole new layer of technical understanding for the lawyers. And until they figure it
        out, it will remain clouds in your coffee.
        Maybe it’s for the best. Once IT gets into the cloud, they’ll want to turn all of the Linux workstations into dumb terminals and rotating a structure will become painfully slow.

        • If you have decent workload management software, your cluster *won’t* be idle most of the time 😉

          • Obviously, you have not worked with a corporate IT department.
            BTW, guess which business unit did not suffer any layoffs?

        • Indeed, RD – back in the late ’70s and early ’80s I worked for a time-share company (before “timeshare” vacations) it was more or less “the cloud” but very structured with high security – we captured major banks as clients and once we had their info we “owned” them.
          To this day whenever I see something that offers this approach I get the shivers because I know how others can use your information.

          • I hear ya but the point of the presentation is that cloud security specialists, like the ones that amazon hire, are experts in their fields when it comes to protecting proprietary information. Most corporation IT departments do not have this level of expertise. The R&D lawyers understood this but the corporate lawyers do not. They’d prefer the gigantic security holes of a microsoft enterprise system to something more secure but new.
            Besides, the stuff that would be done in the cloud from the in silico sciences side would be a complete mystery to the people running the cloud. It doesn’t make sense to anyone until the information has been processed after the files have been retrieved from the cloud and erased from its disks. You can’t be an expert in everything. Even security geniuses have their limits.

  11. IT departments basically exist so that people who have no business using a computer can use a computer. In my company, you’re going to get more knowlegable answers about computers from an engineer than an IT professional. That job is mostly computer maintainance, restricting what you can do rather than expanding it.

    My department has a weekly issue with something our IT people did or failed to do. One was taking down part of the network because they let the UPS connected to the backbone die after beeping for a week.

    I definitely feel the efficiency push where I work. The whole point of lean process is to design the most effective process. The MBAs twist that into wringing more cost out with every pass until the stones are bleeding. Then they throw money at the resulting disaster in product fulfilment.

  12. I did business-to-business sales for ten years, and I never saw any organizations that were as screwy as Pharma. We worked on 21 CFR 11 compliance, and I remember talking to one department head who was actually interested – but didn’t know who to ask to authorize the meeting. “We merged with another company six weeks ago, and I still don’t know who to talk to about not getting my paycheck,” he told me. So much duplication of work teams and management in Pharma, it made my head hurt.

    • Yep, that sounds like pharma all right. The day of the layoff my department completely disappeared and the people who were left in it were scattered to the four winds. I still don’t think they know who they report to.

  13. RD,

    This one’s for you:


  14. omg, drink the bubbly now 🙂

  15. Omg! The BFF is being so gooood to me today. He made dinner. Mussels and baby bok Choy with garlic. I almost feel human.
    No, I am not sharing.

  16. RD,

    Best of luck in getting new work. Much of the same nonsense happens elsewhere too. I worked overseas in a government lab in the 90’s. A change of government led to a new science minister whose minions decided that all our Unix work stations had to be replaced by window PCs. The nonsense was only stopped when it was pointed out that the software we used simply wasn’t available on windows. Not being happy with this, the minions decided that the Unix email system which we used had to be replaced by a Microsoft email system which ended up costing us and the government labs tens of millions of dollars which came out of our budget.

    Regarding “cloud computing”, I think it will only take off once people are comfortable putting in the care of others their pirated movies, porn and corporate secrets.

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