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In which I differ with Derek Lowe over NIH funding

Typical private industry lab circa 2014

Derek Lowe, blogmaster over at In the Pipeline, took issue with NIH Director Frances Collins contention that if the NIH budget hadn’t been cut in the past decade, we might have had an ebola vaccine by now.  I remarked on the Vox article about this very same topic last week.  However, I’m siding with Collins on this topic.  True, he might be using the very scary disease of ebola to make his point but it is a valid one.

To get an idea of what the NIH has been up against, I recommend that readers review the congressional testimony on the ebola outbreak from last week.  I believe it was Anthony Fauci who laid out the problem.  It goes like this:

  1. The NIH identified the need for an ebola vaccine about a decade ago.
  2. (This is the crucial part) The NIH is engaged in basic research.  We are talking very, very basic research.  Like, identifying the genes and sequences and making them available to other researchers, or studying how the virus works and propagates, or figuring out which enzymes chop up the viral proteins, or how the viral proteins are exposed to the rest of the body.  That’s the kind of research the NIH does.  And sometimes, the research is so preliminary that there are mistakes that get published that industrial labs have to figure out when they try to replicate the results in the lab.  Not a criticism.  It happens.  You only have so much money to do the research and sometimes, it’s not enough to double check your results.  I get it.  But it does make it harder for your private industry partners to figure out what’s going on and sometimes means that projects need to take detours to unpack mechanisms and rerun assays and such.  In other words, REAL RESEARCH.  That’s just the way science works, much to the finance industry’s chagrin.
  3. So, the NIH tried to get a private industry partner to help finish the research on the vaccine and develop it.
  4. But during the same decade, private industry was going through a chaotic destructive process brought on by the “patent cliff”.  That is, the blockbuster drugs that fueled industry research suddenly went off patent.  In response, the shareholders who were not about to take a haircut just so some lab rats could continue to do research for them, decided to take the money and run.  That precipitated Pharmageddon, where I and my colleagues got tossed out of corporate labs by the hundreds of thousands.
  5. The NIH couldn’t find a private industry partner until the last couple of years when Glaxo Smith Kline (GSK) decided it would take a risk and start working on one.
  6. In the meantime, in the last couple of years, the Republicans have lost their freaking minds over the budget and would rather let every government institution rot in hell before they would approve any funding.  This is about the same time we wrote a blank check to AIG, and other lords of the finance industry (see Neil Barofsky’s book).  Then the Democrats came up with this great idea of a sequester, you know, to call the Republicans bluff.  And the raving mob that calls itself the Republican party took the deal and slashed NIH funding by 20%.  The Democratic leadership that came up with the boneheaded, backfiring sequester idea should be kept away from sharp objects for their own safety.
  7. So, to recap: NIH needed a vaccine but couldn’t find a private partner for nearly a decade.  Private industry contracted at a time when additional research and development is crucial.  Regular NIH funding is not sufficient for it to develop a vaccine on its own.

This would probably be a good time to insert some Paul Krugmanesque graph that shows the equilibrium between private and public investment in scientific research.  This one should show that when private industry stopped funding research, the corresponding expected increase in public spending was notably absent.

Derek has a libertarian streak and works for one of the last small molecule drug discovery companies in Cambridge.  That’s not necessarily a bad thing but it does skew his perspective just a tad.  Not only that but Derek is operating in the old world order when we tested every therapeutic treatment to death.  That’s clearly not happening with the ebola treatments.  Those suckers have been fast tracked like nobody’s business.  We are treating ZMapp like it’s a cure for ebola when it’s nothing of the sort.  It’s just that it’s the only thing we’ve got.  ZMapp is so early in development that back in the old days of real drug discovery, it might have been killed in a project portfolio review before it ever made it to development.  And the vaccines?  Well, normally, they’d go through many stages of development and testing for safety, efficacy, and side effects with an expanding number of trial recipients at each stage before it was approved by the FDA.  Forget that.  In this epidemic in West Africa, with number of exposures increasing exponentially, no one has time for these niceties (though I can just see some lefties screaming about how we killed West Africans with an untested vaccine that triggered a cytokine storm or autoimmune disease.  Wait for it.  You know it’s going to happen.  There will probably be a movie about it featuring some ruggedly handsome Liam Neesom type and a earnestly beautiful lady scientist detective out to uncover the awful truth of corporate exploitation of poor third world citizens.).

The real world is not so simple but there definitely is money at the bottom of this mess.

I’ve worked on both sides of the problems in both industry and in academia, if only briefly.  But I got a good look at what it’s like to do research on NIH grant money and it’s not pretty.  Most of a principal investigator’s time is spent preparing grant applications.  It’s very bureaucratic and, I suspect, very political.  If there isn’t a retrospective analysis on the amount of grant money that goes to the Ivies that leave the rest of the academic labs starving for funds, there really should be.  Not every breakthrough has to happen at Harvard.  The polio vaccine, for example, was developed in Pittsburgh.  Oh, yeah, how many of you knew that Jonas Salk worked for the University of Pittsburgh? True story.

And yet, it was about a year ago that I got a call in my office at Pitt from a researcher in the immunology group who had just lost her job because of the sequester.  It was last year at about this time that we had to cut back sharply on ordering chemicals and lab supplies for my lab because grants were on hold, also due to the sequester.  Even today, I see positions at Pitt for the kind of work that I used to do but the hours are part time.  Really??  You expect scientists to do protein production, extraction and crystallization experiments on a part time basis?  That’s the craziest thing I have ever seen.  You can’t just interrupt an experiment half way through the week because you’ve run out of hours.  That makes me think that the people posting the positions aren’t serious about how many hours they expect the researcher to be available.  It’s deceptive and weird and unrealistic.  But that’s life on soft money.  Here today, gone the next.  Yet the cells still need to be fed, lysed, protein collected, spun, purified, etc, etc, etc.

Friends, Americans, countrypersons, this is no way to run a research infrastructure.  Ok, sure, it’s the way to run a research infrastructure if you don’t want to do it like Americans used to do it.  If you are content to run a research infrastructure like Bolivians do it, fine, do it this way.  But don’t complain later that nothing of significance happened on the science front from 2008 onward.  Don’t complain that the NIH is not telling the truth about funding.  It can’t be all things to all people without a steady funding mechanism that isn’t going to be subject to violent shocks brought on by crazy people who get elected to Congress.

Here’s the bottom line.  If liberals expect the NIH to do all of the things that they *think* it already does, it needs more funding.  It needs waaaaaaaay more funding than it already has.  It needs as much funding as private industry used to pump into its own research coffers but no longer does.  It needs billions and billions more.  It has to become what private industry used to be but no longer wants to be.

And if Republicans are committed to free enterprise at all costs, it’s going to have to get tough with private industry drug discovery and force it to take on research that it sees as unprofitable.  It needs to have a serious talk with the bonus class and shareholders about greed at the expense of public health.  Isn’t that what the GOP is all about?  Morality?

That’s just the honest truth.  The NIH is not private industry.  If we want the NIH to replace private industry, which has abandoned certain, critical research areas because it can’t make the kind of profits that shareholders demand nowadays, we need to put more money into the NIH and fund researchers properly and seriously.  That is the point that Frances Collins has been trying to make.

Liberals have a complete misunderstanding of what the NIH does or is capable of doing.  Libertarians have an inflated view of what private industry can do, sometimes because they are living in one of the last holdouts of productive private industry drug discovery (that could end at any time, so don’t get too comfy, Derek).  But once you have lived in both worlds, you can see what a shambles the whole system is.  It’s unsettling and alarming.

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.

 

 

More on Drug Discovery and public funding

Following up on the last post on Virtually Speaking’s recent episode featuring Dean Baker and his comments on drug discovery, I’ve had a nice conversation with Jay and I think we are a little closer to understanding what’s going on here.  In some sense, we may have been talking past each other, in another sense, there are still some engrained biases there that the left will need to fight its natural impulses in order to contain.  But it is all good.

So, in the interest of fairness, I am posting a link to Baker’s proposal to a public funding mechanism for drug discovery.  I confess that I haven’t had time to read it yet, what with moving and work related activities, making sure Brook is studying for her finals, and driving back and forth between PA and NJ, so I’m going to hold off critiquing it until I do.  However, I will say that any policy proposals that don’t involve the input of people who actually have the experience of drug discovery are probably not going to work very well.  After all, we’ve had a couple of decades of the MBA class restructuring on a regular basis without the input of their R&D staff and how did that work out?  We do have opinions and are well trained in the scientific method, so, you know, take advantage of our expertise before you set up some new system that might be as unworkable as the old one was.

Here’s the link to Dean’s Financing Drug Research: What are the Issues?   I just noticed that it was written in 2004.  At this point, given the last decade of craziness, it’s out of date and due for a rewrite.  I mean, for one thing, there really isn’t an American drug discovery industry anymore.  There are only remnants and a whole lotta unemployed chemists with lots of time on their hands.

And here is a recent post from Derek Lowe on the subject of The Atlantic’s recent article, How Drug Companies Keep Medicine Out of Reach.  Derek touches on some of the mythology surrounding the drug discovery process. Says Derek:

At some point, the article’s discussion of delinking R&D and the problems with the current patent model spread fuzzily outside the bounds of tropical diseases (where there really is a market failure, I’d say) and start heading off into drug discovery in general. And that’s where my quotes start showing up. The author did interview me by phone, and we had a good discussion. I’d like to think that I helped emphasize that when we in the drug business say that drug discovery is hard, that we’re not just putting on a show for the crowd.

But there’s an awful lot of “Gosh, it’s so cheap to make these drugs, why are they so expensive?” in this piece. To be fair, Till does mention that drug discovery is an expensive and risky undertaking, but I’m not sure that someone reading the article will quite take on board how expensive and how risky it is, and what the implications are. There’s also a lot of criticism of drug companies for pricing their products at “what the market will bear”, rather than as some percentage of what it cost to discover or make them. This is a form of economics I’ve criticized many times here, and I won’t go into all the arguments again – but I will ask:what other products are priced in such a manner? Other than what customers will pay for them? Implicit in these arguments is the idea that there’s some sort of reasonable, gentlemanly profit that won’t offend anyone’s sensibilities, while grasping for more than that is just something that shouldn’t be allowed. But just try to run an R&D-driven business on that concept. I mean, the article itself details the trouble that Eli Lilly, AstraZeneca, and others are facing with their patent expirations. What sort of trouble would they be in if they’d said “No, no, we shouldn’t make such profits off our patented drugs. That would be indecent.” Even with those massive profits, they’re in trouble.

And that brings up another point: we also get the “Drug companies only spend X pennies per dollar on R&D”. That’s the usual response to pointing out situations like Lilly’s; that they took the money and spent it on fleets of yachts or something. The figure given in the article is 16 cents per dollar of revenue, and it’s prefaced by an “only”. Only? Here, go look at different industries, around the world, and find one that spends more. By any industrial standard, we are plowing massive amounts back into the labs. I know that I complain about companies doing things like stock buybacks, but that’s a complaint at the margin of what is already pretty impressive spending.

The point is that drug discovery ain’t rocket science.  It’s much, much harder.  Are there ways to make it easier and less expensive to the average consumer?  Yeah, probably, but it’s still bloody hard and in some respects, the left has as much to answer for as the right does when it comes to the cost and expense of developing drugs.  If we’re all in this together, then the left has an obligation to learn all that it can about the mechanisms of drug discovery and who is making a fortune on drug failures as well as successes because we know that the right isn’t going to do it.  Let’s be better than them.  M’kay?

 

 

Talking us down from the glyphosate ledge

Glyphosate. Not keeping me up at night.

Glyphosate is now the new cyclamate and we’re all supposed to be terrified to use it in agriculture.  Oh, please.  Check out this analysis of the glyphosate study by Derek Lowe at In the Pipeline, Is Glyphosate Poisoning Everyone?.  Here’s the money quote:

Now, that presumably sounds extremely detailed and impressive if you don’t know any toxicology. What you wouldn’t know from reading through all of it is that their reference 121 actually tested glyphosate against human CYP enzymes. In fact, you wouldn’t know that anyone has ever actually done such an experiment, because all the evidence adduced in the paper is indirect – this species does that, so humans might do this, and this might be that, because this other thing over here has been shown that it could be something else. But the direct evidence is available, and is not cited – in fact, it’s explicitly ignored. Reference 121 showed that glyphosate was inactive against all human CYP isoforms except 2C9, where it had in IC50 of 3.7 micromolar. You would also not know from this new paper that there is no way that ingested glyphosate could possibly reachlevels in humans to inhibit CYP2C9 at that potency.

In the pharma lab, if a compound had an IC50 of 3.7 micromolar against a target, we’d have to be desperate to call it a “hit”.  That level of activity means you’d have to choke down a lot of chocolate cookies before you’d be even mildly affected.

So, you can stop worrying about glyphosate poisoning.  That doesn’t mean everything in the world is safe to consume.  It’s just that glyphosate is no dioxin and you won’t have to superfund site a farm that uses it.

Lowe also has a post on the cost of cancer drugs that is worth reading.  It gems fairly nicely with my cynical theory of the current pharma business model, which goes like this: Once upon a time, big pharma made drugs for all kinds of ailments, like heart disease, schizophrenia, depression, reproductive health, antibiotics, diabetes, pain, inflammation, etc.  But over the last 30 years, it has become increasingly more difficult to get those drugs to market for a variety of reasons I won’t go into here.  Suffice it to say that the FDA doesn’t approve very many small molecule drugs anymore.  Like virtually none.  A pharma can spend a lot of money on research only to have a drug shot down at the approval stage.  So, how does a drug company make money if it can’t sell drugs?

Easy.  It concentrates on cancer and orphan drugs.  Orphan drugs are for diseases that are relatively rare.  For cancer drugs, the path to profit is pretty straightforward.  The patients are desperate. They’ll pay what the market will bear and then some.  Will they mortgage their houses?  Yeah, probably.  So, the market is there.  But it gets better.  Cancer drugs are fast tracked for approval and no one is overly concerned with toxicity.  In other words, there won’t be class action lawsuits because patients are grateful for any extension of life they get.  Even if the patient dies, their families are likely to consider their treatment as advancing the knowledge of science.  No one complains.  If you’re a bean counter, oncology drugs are as good as it gets.  They’re profitable, quickly approved, they don’t have to be perfect and no one will hold you accountable.  It’s probably the same situation for orphan drugs.

This is the financier’s mindset at work.  R&D people don’t think like this.  But in the end, there is a ceiling to the amount of money we as a society are willing to pay for potentially lifesaving drugs and  we are now up against it.  Meanwhile, if you are suffering from any other ailment, like bipolar disease or osteoporosis or some flesh eating bacterial infection, you’re going to be stuck with older drugs that are quickly becoming generics.  The good news is that the generics will be cheaper, well, at least for a little while longer.  I don’t think that can last as there won’t be enough profit in generics to keep the production facilities up to FDA standards. I can easily imagine some production facilities being taken offline a la the rolling blackouts of the California energy crisis 10 years ago.  Some jerk generics traders are going to be yucking it up about Granny not being able to afford her cholesterol lowering drugs.  Call me paranoid but as far as I know, there’s nothing to stop such scenarios from taking place and I wouldn’t be surprised if it’s already happened.

At some point, the price of generics will start to rise and in some cases, they haven’t really dropped all that much yet.   There won’t be a steady stream of new and improved drugs coming from the pipeline.  It will be more of a thin trickle.  The public has spoken.  It doesn’t want me-too drugs even if they are better than what’s already on the market, and it doesn’t want any drug that’s less than 100% perfect and free from all side effects.  Whether this combination of financier morality and public skittishness is good for medicine, science or society are questions we haven’t even considered yet.  No one, it seems, except the displaced scientists from Pharmageddon seem to be discussing those issues.  Someday, the Ezra Kleins and Duncan Blacks will wonder how that happened but it’s already almost too late to do anything about the coming Dark Ages of pharmaceutical medicine.

So, if you’re rich and you have cancer, you’re probably going to be Ok.  If not, well, it’s just another symptom of being in the 99%.

Pharma can’t find post-doc STEM graduates to do incredibly boring paperwork jobs, hiring managers say

Derek Lowe at In the Pipeline asked for an eye catching headline to summarize a new labor report on the dismal fate of STEM graduates so I thought I’d give it a shot:

The knowledge-intensive pharmaceutical industry had the highest reported difficulty in hiring top talent of the 19 industries featured in PwC’s 2012 Global CEO Survey. CEOs identified talent gaps as one of the biggest threats to future growth prospects.

Research conducted by HRI, including a survey of human resource and R&D executives at U.S. biopharmaceutical companies found (that) fifty-one percent of industry executives report that hiring has become increasingly difficult and only 28 percent feel very confident they will have access to top talent.

Of course, the workplace is not stagnant and the demand for certain skills is always evolving. Seen this way, the data suggest that pharma execs may want the sort of talent that is not on the sidelines or simply clamoring for a different opportunity. For instance, 34 percent say that developing and managing outside partnerships is the most important skill being sought among scientists. . .

Well, it all makes sense to me.  What pharma wants is not scientists, they want lawyers to negotiate contracts and efficiency experts to break down each experiment into a set of easily digestible tasks.  That’s not really science anymore because the ability to think for oneself, analyze procedures and take advantage of serendipity is lacking but nevermind the counterintuitiveness of it all. Chemists and molecular biologists didn’t spent 12 extra years doing lab work in order to push papers around.  They planned to actually work in a lab, not that there’s anything wrong with that.

Funny how you have to tack that apology onto the end of the sentence when you are referring to people who actually get their hands dirty.  We’re working with someone else’s values when it is assumed that the thing scientists would prefer above all things is to work their way out of the lab and never have to touch a chemical or wear a labcoat again.  Well, anyway, they said they don’t want people like that anymore.  You know, those scientific malingerers who hide out in university corridors waiting for a hit of the Journal of Medicinal Chemistry or whiff of stewing e.coli.

This is what happens to an industry that gets taken over by the brain trusts on Wall Street.  They think that any industry that’s not finance can be outsourced and managed by people a little bit like them but who simply have more experience in the lab.  I hope they’re not counting on fresh out of school Harvard PhDs to this work because even they need about a decade’s worth of seasoning before they even know who to manage or what to do to make a project work.

Come to think of it, you don’t need PhDs to do this stuff.  Why not just hire any science type sucker who needs to make ends meet?  We all know how to use Excel and PowerPoint and we’ve all got experience slogging through the badly implemented SAP systems that the executive branch is so proud of.  You don’t need to go to an Ivy League university for 12 years to be a scientifically literate corporate drone.  A BS level employee with a 2 month crash course in drug discovery could probably do it.  I mean, that’s how it’s done on Wall Street, right?  You take some overprivileged  23 year old recent graduates from Princeton and teach them how to do finance in 2 months before they’re set loose on the world.  What could possibly go wrong?

Flee from science majors, little children!  Flee!

In another sign of the times, Derek posts on yet another company that’s had to lay off early stage discovery staff in order to move their two lead projects into development and clinical trials.  That means, the dedicated chemists, drug designers, biologists, pharmacologists, etc will have to pack up their pipettes and find another job.  They probably *won’t* be able to work on the same kind of project again and use their expertise. There goes the mortgage on the house, the car payments, the college funds.  Imagine having to do this every couple of years- if you’re lucky enough to actually work in a lab and not tied to a chair in Massachusetts managing people in Shanghai.

I hope it’s not to much longer before our nation’s leaders realize they’ve been lied to about the promise of “entrepreneurship” in biotech.  The initial overhead costs are among the highest of any industry and a payoff is unlikely.  The big pharmas that are preying like vultures on the promising tidbits on the skeletons of little start ups are the same companies that couldn’t get blockbusters to market after several rounds of M&A and sinking billions of dollars into very badly managed R&D departments.

Believe it or not, there are lot of scientists who are not dying to relocate to Cambridge to work in the offices of big pharma.  The ones who do go to Cambridge and South San Francisco are just postponing the inevitable.  The rest of us would rather take pay cuts for some modicum of stability or get out of science altogether.

Whatever.  What the world needs now is a good plague to wipe out the aristocrats and middle men and let the scientists get on with it without any further interference.

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

Zombie Symmetry shows what’s involved in drug discovery these days:

Big Pharma and the power of a union

French union scientists at Toulouse do a haka to protest salary and position cuts.
{{sniff}} I am so proud!

Derek Lowe at In The Pipeline wrote recently about French drugmaker Sanofi’s recent plans to close some sites in France.  I’ll get to that in a minute but first a little background.

A few weeks ago, Sanofi announced that it would be closing some French sites, the biggest site would be at Toulouse.  The closure would have put approximately 2300 scientists out on the unemployment rolls.  The Ministry that handles labor and unemployment had a fricking fit:

Besides unions, Sanofi has gotten an ear full from some government officials. With France’s economy struggling, the fact that Sanofi’s mother country was absorbing more of the pain, has not set well. French Productive Recovery Minister Arnaud Montebourg told senators when the cuts were first leaked: “Sanofi showed up at the ministry to tell us they were planning several thousand job cuts. Couldn’t you have said that earlier on? Last year you made €5 billion ($6.1 billion) in profits.”

And I’m sure that Sanofi would have cut elsewhere, if they had anywhere else to cut.  Last year, the company laid off all of the scientists at their main site in the US that was located in Bridgewater, NJ.  A couple dozen jobs were rescued and sent to the Cambridge, MA site, which is small, cramped and inadequate.  The rest of the projects were distributed to the French sites.  And do you want to know WHY the work went to the French sites and not to China (at least not yet)?  I’ll tell you why:

THE FRENCH SCIENTISTS ARE PROTECTED BY A UNION

Their union is pretty damn good too.  You could take every project away from them and have them just occupying the sites and playing tetris all day and the company would still have to pay them.  So, any time the company felt like research was being too much of a money pit, they took it out on the US workers until there weren’t any left.

This time, the unions threatened to strike and the French Productive Recovery Minister told the company that dumping French scientists on the labor market and relying on the government was not an option.  Usually, the companies who do business in France lay scientists off through attrition or generous early retirement packages.  A straight layoff , although rare, is still heavenly by American standards with terminated employees getting up to 80% of their salaries for 2 years and then able to go on the French public assistance program after that.  AND you don’t need to shell out half your unemployment on COBRA.  So, pretty sweet deal even if you’re being laid off.  You have time to find something else or go back to school for retraining or emigrate to Canada.  Your life isn’t thrown into an instant and chronic crisis.  And THAT, in turn, helps stabilize the rest of the economy.  The more people who can spend and keep demand up, the less of a hit the economy takes in newly unemployed people.

Anyway, it was still looking pretty grim for the French scientists until this week.  It looks like the Productive Recovery Ministry and the unions had an impact.  From Derek’s post:

here’s the announcement itself. And maybe this is my first impression, but compared to what’s gone on in other Sanofi sites (like Bridgewater), this one comes across like a shower of dandelion fluff. No reduction in the number of sites, no actual layoffs – just 900 positions to phase out, mostly via attrition, over the next two years. The Toulouse site is the only loose end; that one is the subject of a “working group” to figure out what it’s going to do, but I see no actual language about closing it.

Here’s more from FiercePharma’s article on the cutbacks in France:

A key official in France is keeping up pressure on Sanofi about its planned work force reductions in the country, sticking to the position that the drug giant ($SNY) hasn’t done enough to protect jobs. And French Industry Minister Arnaud Montebourg makes clear in reports today that he isn’t satisfied with how the company plans to secure the future of its R&D site in Toulouse.

Montebourg has been a thorn in the side of Sanofi. Early this week Sanofi softened its stance on job cuts in France, saying the company would seek to shrink its work force in the country by 900 jobs through early retirements and voluntary moves and transfers in the next few years, as opposed to the 2,300 to 2,500 jobs at the company previously estimated to be on the chopping block. Yet the minister and others keep harping on Sanofi’s unresolved plan for its Toulouse site, where 600 additional jobs hang in the balance.

Sanofi wants to part ways with research in Toulouse, and said earlier this week that it would work with stakeholders in the coming months to solidify plans to keep the operation alive, Reuters reported. That too fell short with Montebourg and unhappy Sanofi workers and labor officials.

“Trade unions are right to say this is too much,” Montebourg told BFM television, as reported by Reuters. “The government thinks this is too much and we want guarantees for Toulouse.”

Sanofi CEO Chris Viehbacher, who has reportedly met with the industry minister, has found resistance in his strategy to double down on productive R&D centers while making cutbacks at those that fail to meet expectations.

You know, if Chris Viehbacher wanted to preserve the company’s most productive sites, maybe he should have kept the US scientists on their tree-lined campuses instead of keeping them in a high state of suspense for several years, terminating their projects and then stupidly laying them off and closing the site.  No wonder the French Ministry doesn’t believe a single thing he says.

So, there you go, folks.  If you want to stand up to the bonus class and save your jobs, you need to get a union and the government behind you.  Or maybe just the government behind you.  You don’t need to work 24/7 like a maniacal drone on crack, cranking out work and trying to impress everyone working like crazy, singing, “I really need this job.  Oh, God, I need this job” to guys on Wall Street who don’t give a shit anyway.  No, you have your union representatives negotiate a contract that makes it extremely painful for the company to drop its commitment to you.

Not only that, but the union has to be very, very active and visible, like standing outside the cafeteria, handing out grievance pamphlets and making its presence very known to the management.  Imagine going to lunch to eat your company subsidized baguette, custom prepared omelet and glass of red wine and being greeted at the door by a union person dissing the management and getting away with it.  (Oh, yes, it really happens, I saw it with my own eyes.)  Take a look at that picture.  Does that look like a bunch of broken human beings, cowering under the whip they’ve been forced to kiss, cringing in fear of being fired for speaking up or fighting for their rights?  Damn straight it doesn’t.

That’s why I keep saying that drug discovery will survive in Europe. They’ll have an infrastructure in France and Germany and the expertise that is acquired from having stability and continuity of uninterrupted research.  They’ll be able to keep pace with this rapidly changing explosion of biological discoveries while thousands of US scientists will be trapped in routine, unchallenging CROs or having their expertise rotting from disuse.  Maybe they won’t be as productive as the US researchers used to be or as ingenious as possible but, by golly, they may be all the world has left unless and until the Chinese and Indians can stabilize their business environment and take the lead in research.  It’s not easy and it will take some time before that happens.  The finance guys are going to have to take an old, cold tater and wait, not something they’re good at.  They’re going to be mad that they can’t transform our salaries into their bonus gold, but such is life.  The French government is finally standing up to them and saying “Non”.  In this case, the unions are actually doing them a favor, giving them an excuse to keep the technological expertise in the country and giving it an edge when the recession finally eases up.  The government will soak the corporations for salaries, not the workers for absolutely everything.

The bad news is that now that Sanofi has been forced to scale back their cutback plans in France, they’re going to have to take it out on their remaining employees elsewhere, like their site in Cambridge, which is already tiny, and their exploratory facility located in Tucson, Arizona.

So, for those of you professionals who are watching in horror at what happened to the scientists in this country, take note: get a union.  The problem of unemployment among us is not structural.  There are plenty of us and many of us are willing to relocate or work from home.  The problem is that the big guys don’t want to pay us for our expertise.  So, they’re going to keep spreading this lie that they can’t find enough qualified workers.  The real problem is that OUR government is not on OUR side.  The Obama administration would rather this country lost its technological edge and make precariats of us all than to stick up for us when the finance guys calculate their bonuses based on how many R&D bodies they can chop.

Sad but true and this story is proof.

Debunking the myth that the NIH discovers drugs and industry just exploits it

Derek Lowe describes how the drug discovery process really works and why critics who perpetuate the myth that the NIH discovers targets and drugs before the pharma industry ruthlessly exploits the taxpayer don’t know what the hell they’re talking about.  Here’s a snippet but if you’re interested in this kind of thing because you don’t know much about it, you should read the whole post:

 I think I’ve hit on at least one fundamental misconception that these people have. All of them seem to think that the key step in drug discovery is target ID – once you’ve got a molecular target, you’re pretty much home free, and all that was done by NIH money, etc., etc. It seems that these people have a very odd idea about high-throughput screening: they seem to think that we screen our vast collections of molecules and out pops a drug.

Of course, out is what a drug does not pop, if you follow my meaning. What pops out are hits, some of which are not what they say on the label any more. And some of the remaining ones just don’t reproduce when you run the same experiment again. And even some of the ones that do reproduce are showing up as hits not because they’re affecting your target, but because they’re hosing up your assay by some other means. Once you’ve cleared all that underbrush out, you can start to talk about leads.

Those lead molecules are not created equal, either. Some of them are more potent than others, but the more potent ones might be much higher molecular weights (and thus not as ligand efficient). Or they might be compounds from another project and already known to hit a target that you don’t want to hit. Once you pick out the ones that you actually want to do some chemistry on, you may find, as you start to test new molecules in the series, that some of them have more tractable structure-activity relationships than others. There are singletons out there, or near-singletons: compounds that have some activity as they stand, but for which every change in structure represents a step down. The only way to find that out is to test analogs. You might have some more in your files, or you might be able to buy some from the catalogs. But in many cases, you’ll have to make them yourself, and a significant number of those compounds you make will be dead ends. You need to know which ones, though, so that’s valuable information.

That’s just the start of the problem as Derek goes on to point out.  This is usually where the drug designers get involved, sifting through the information that comes from the screens, clustering the compounds that show activity, doing searches on in-house and commercial databases, finding the common features of the hits to determine if there’s a reason why they’re active, and proposing modifications to those lead series (that the chemists will ignore).  You do this on enough projects and you become a very good pattern spotter without really trying.  But that was only a small part of my job.  Most of the projects I’ve been involved in go on for years.  It’s a very iterative process and sometimes, the project takes off on tangents  It’s like untying a giant knot with lots of little subknots that sometimes need to be solved first.

The bottom line is that as valuable as the NIH contribution is, it’s usually the 1% inspiration that leads to the drug industry’s 99% perspiration.

Politicians should spend a little time interviewing the drug discovery people.  I don’t mean the executives or the lobbyists.  I mean the people who actually do the work.  It appears that there is a lot of mythology to dispel still.  And without a more complete concept of how drug discovery works, it’s difficult to craft policies to make pharma research work for patients, government and businesses.

If I might make a suggestion to Derek, visual aids might be useful.  Just dig a couple of slides from your latest pre-project team meeting and modify the names of the targets.  People will not really grasp what is involved until they see it.

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