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The Baseless Fabric of This Vision

Not everyone is going to sit still and listen to someone from GlaxoSmithKline talk about how to most effectively deploy chemists (and wonder where more of them might be coming from). If you’re up for it, here’s the article at Drug Discovery Today. It’s not trying to hide the situation, though (links added for the original references in the manuscript):

The number of scientists employed in pharmaceutical R&D has decreased substantially over the past decade as a result of mergers, acquisitions and general economic constraint. In the UK for example, the numbers have fallen 28% from a peak of 32,000 in 2007 to 23,000 in 2013. Furthermore, within our industry there is a growing focus on biological approaches such as monoclonal antibodies or cell and gene therapy to target very specific patient phenotypes, stimulated by our expanded knowledge of the human genome. For example, in 2015, one third of new drugs approved in the US by the Food and Drug Administration (FDA) were antibodies, peptides or enzymes, compared with about a quarter in 2014 (Ref #3 C&EN). We can therefore reasonably assume that the number of medicinal chemists in the pharmaceutical industry in the UK has decreased by about a third since 2007

At least. The article goes on to talk about GSK’s strategy for chemistry, and this part might be a hard sell in say, North Carolina:

Within GSK R&D a thorough evaluation led us to a core strategy of maximising the cost effectiveness of our chemists by investing heavily and continuously in professional development and providing a framework for them to focus on higher value and innovative activities. Investing in chemistry talent is an important part of our strategy to reduce the high levels of drug discovery attrition which have been so problematical within our industry.

The rest of the piece reads a bit like a presentation from the company’s HR department, to be honest about it, as it goes into detail on how the company identifies and develops chemists. None of it sounds particularly bad on paper, but a person of cynical bent would note that sounding good on paper is a major design feature of all these things. I do, however, give the author credit for this ending:

Ultimately, however, the success of the model will be judged by the destination, which in our industry tends to be some 10 years after the medicinal chemistry costs are spent. Therefore, while an energised and motivated workforce with a great demographic holds much appeal, the ultimate effectiveness will be determined by the number of drug approvals that we achieve over the forthcoming years.

And there’s the problem. Very few Big Strategies at a given company last for ten years, no matter who’s in charge. Very few people are even in charge for that long, for that matter, and the next set of people will have their own ideas about things should be run. So I really have to doubt if anyone has ever seen a consistent large-scale strategy through in this business for ten years under modern conditions. The way to check would be to pick any given year, and then go back ten years and look at the slide decks and management presentations, asking yourself “Do these artifacts bear any resemblance at all to what really happened?” Ten years is a good estimate for the amount of time you have to wait to see effects downstream in the clinic and in approvals, but that’s an awfully long time for a PowerPoint slide deck to remain relevant.

Personally, I’ve lost count since I started work in 1989 of the various revamps, overhauls, re-orgs, re-alignments, and Big Total Changes I’ve seen. One that I remember fondly featured the slogan “No More Business As Usual”, and after a couple of months, people starting putting a comma after the “No”. When I got to the Wonder Drug Factory in 1997, all the ID cards carried the logo “Vision 2010!”, which was the company’s Seldon Plan for becoming a mighty force by that distant year. The world had other ideas, at least for us. By 2010, those of us who were fortunate enough to be working all were scattered to different companies entirely, and the buildings we we’d been working in didn’t even belong to the company any more.

Alas, all planning! Or at least all big, overarching, multiyear planning. Back in the late 80s, you used to hear about companies in Japan that had business plans for the next fifty or hundred years. I have to think that these were apocryphal tales spread by consultants, who wanted to spread fear and doubt in order to be hired for their own fearsome planning abilities. I mean, how idiotic would you have to be to seriously attempt any useful strategy over that time span? Remember, this was in the era of Japan Is Coming to Rule the World, itself an interesting artifact of long-range thinking: if you’d asked a bunch of consultants back then to predict Japan’s economy over the next 25 years, I’m pretty sure that what really happened (flatter than a sushi mat) would never have made the list, not even in the backup slides.

So while I may grit my teeth a bit at hearing GlaxoSmithKline’s strategic chemistry thoughts, that last paragraph is the one that turns around, like Prospero in The Tempest, and dismisses the rest of the article, “cloud-capp’d towers, gorgeous palaces, solemn temples” and all.

51 comments on “The Baseless Fabric of This Vision”

  1. Gsker says:

    The one thing GSK knows how to do with chemists is to fire them. Maybe soon we will have an R&D organization without the R&D.

  2. Peter Kenny says:

    I recall a ‘Great Expectations’ initiative and somebody making the observation that the novel of the same name started among tombstones. There is a quote from Macbeth (Act 5, scene 5) that may possibly be appropriate:

    “To-morrow, and to-morrow, and to-morrow,
    Creeps in this petty pace from day to day,
    To the last syllable of recorded time;
    And all our yesterdays have lighted fools
    The way to dusty death. Out, out, brief candle!
    Life’s but a walking shadow, a poor player,
    That struts and frets his hour upon the stage,
    And then is heard no more. It is a tale
    Told by an idiot, full of sound and fury,
    Signifying nothing.”

    But let’s not offend those grinning HR types with our negative thoughts. Instead let us give thanks for the seminal contributions of property forecast index (see blog post linked as the URL for this comment) and the 4/400 rule.

  3. exGlaxoid says:

    Having worked there for almost 20 years, the current management at GSK has success removed all of the best chemists (as judged by actually getting a drug to market), virtually everyone there who had any success in the last 15 years was laid off or treated so badly that they left. That includes people who discovered most of their virology drugs (mostly NC scientists), oncology drugs (which they then sold) (mostly NC scientists), and many of the best UK scientists who discovered the multitude of drugs there in Neuro, asthsma, anti-infectives, and other areas. While the other businesses in consumer and vaccines are doing OK, the previous decisions to sell BW’s consumer products back in 1996 now appears to have been a terrible idea, as does some other BW and Glaxo older compounds sold off, which eventually ended up at Turing and other places.

    1. Peter Kenny says:

      Now I understand Property Forecast Index…

    2. Bagnar says:

      I’m too young to have known the chemists you’re talking about, but I spend a year in Stevenage (UK), at GSK’s research center and I met here some incredibly good chemist.
      Old and young, to be fair.

      So, some of them may have been laid off (according to you, I can’t confirm it), but some excellent ones have arrived too.
      But, I agree with you, and many people in R&D too, the current management is hard to understand. (The “smart lab” thing is a good example of it. Such a wonderful idea to put biologist and chemists at the same bench, moreover if you introduce the “hot bench” system… )

      Anyway, I had a wonderful year overthere, so even if the “best chemists” are gone, those left are still excellent and I learnt a lot !

    3. PFI says:

      Perpetual Futility Index. That pretty much characterizes GSK over the past 10 years, thanks to poor leadership making consistently bad decisions and misguided strategy that’s poorly executed. The DDT article reads like the latest “we’ve got it right this time” justification for reorganizing drug discovery practice into oblivion. At least the “flex chem” model has for the time being stabilized medchem layoffs, though ironically it goes full circle to the pre-DPU pipeline structure. However, the ultimate trajectory of GSK, post Sir Witty, seems destined for a different reorg – merge or split.

  4. Curious Wavefunction says:

    Also, “The best lack all conviction while the worst are full of passionate intensity” might be relevant here.

  5. Pharmandias says:

    The talk of all these long-term plans brought to mind another instance where time triumphed over similarly ambitious claims.

    I met a traveller from an antique land
    Who said: “Two vast and trunkless legs of stone
    Stand in the desert. Near them, on the sand,
    Half sunk, a shattered visage lies, whose frown,
    And wrinkled lip, and sneer of cold command,
    Tell that its sculptor well those passions read
    Which yet survive, stamped on these lifeless things,
    The hand that mocked them and the heart that fed:
    And on the pedestal these words appear:
    ‘My name is Ozymandias, king of kings:
    Look on my works, ye Mighty, and despair!’
    Nothing beside remains. Round the decay
    Of that colossal wreck, boundless and bare
    The lone and level sands stretch far away.

  6. As a great man once said, “success is the ability to go from one failure to another with no loss of enthusiasm.”

    1. AF says:

      Churchill??

      1. Yep – full marks. Another one from the same source and that would seem to hit the mark: “It is a mistake to look too far ahead. Only one link in the chain of destiny can be handled at a time.”

        Since we’re at it, Yogi Berra also has a good one: “It’s tough to make predictions, especially about the future.”

  7. anon the II says:

    I’m trying to understand the motivation for writing an article like that. Is it just to get a pub? Was he coerced? Who’s it for?

    I like the clever use of the terms “potential” and “early”. We know what that means.

    It’s basically an “it sucks to be a chemist these days, but I’m doing the best I can” kind of article. Why bother?

    1. Alastair says:

      As a GSK stock owner I can only hope that it was not written on company time!

  8. pete says:

    ..and after TMTC* years of revisioning in pharma/biotech, you could also try this placement of the comma: “no more business, as usual”
    * too many to count

  9. watcher says:

    Unfortunately, not able to see the article without paying, and doubtful it’s worth it. But the author is a non-PhD chemist in the UK who has (remarkably) risen up the ladder to a very senior position in GSK. Within his therapeutic area (Pulmonary) he tends to be skeptical of most ideas from the US while being very protective of his UK resources, in particular the chemists in his line. Why did he do this? Perhaps to make a point to those in charge of total resources at GSK and other companies that small molecule drugs do not make themselves. He has little to lose at GSK in his current position as he’s not likely to go further up the line unless they’d remake traditional technical departments instead of focusing on therapy area structures. Might that happen…well GSK is looking for a new (hopefully experienced) CEO to replace Sir Andy Witty, and there then is no way to know what a new regime might bring!
    Of course the author would discuss the loss of jobs in the UK because it is under his nose every day. However, lets not forget what has happened to the company’s other major R&D facilities in other countries over the last 10 years covering much of the current CEOs term.. The site in Verona Italy was sold; many people were dismissed from jobs immediately, and more over time. There have been numerous “downsizings” for various purposes….anticipating loss of revenue due to accusations made about Avandia, raise extra cash to pay for acquisitions such as Sirtrus which has become funds lost down a dark hole, reconfigurings and refocussing of R&D, outsourcing of chemistry to India and China. Not long ago, almost all of R&D exited the North Carolina site at RTP. And now in the Philadelphia area there is a consolidation of the two R&D sites that used to consist of full buildings and overflowing parking lots that are now half empty into only one of the existing footprints without any new immediate buildings.
    Yes, where do the new drugs come from? Or does GSK make any at all and just become a marketing entity along with OTC and vaccines on the side? Those holding company stock in addition to those working there might hope the new CEO will reverse the trend, but it’s certainly not going to be what it was 10+ years ago very in a conceivable time frame.

  10. BankruptinNC says:

    GSK has been steadfast in at least one strategy over the last 15 years…corporate fraud, Paxil, Avandia shenanigans, GMP/quality violations, supplying prostitutes to Chinese doctors etc etc. It is amazing that the US Dept. of Justice can reach across the world and indict FIFA officials, but this company gets away with $1Billion+ in fines, Consent Decrees, shut down of plants, etc etc without a SINGLE executive going to jail. One whistleblower walked away with $93Million, and thousands of other poor schmucks lost their jobs and retirement savings due to all this fraud. And all those Corporate Vice Presidents of Quality, Medical and Sales VPs all got away scott-free with millions in bonuses. ‘Murica, y’all!

  11. annonie says:

    BankruptinNC:
    At least get your fact right. GSK did nothing wrong with Avandia. A meta-analysis done by a third party who had actually consulted with another company was done that forced very limited use of the compound. Ultimately, an ongoing study discounted the meta analysis but by then the opportunity to make anything was lost.
    And how did you lose retirement funds? Anything in your 401K or pension are still be yours to claim if you leave on good terms.

  12. SmallMoleculeGuy says:

    I think it is important to put those statements into a broader context. Sir Andrew and his team have been attempting, with evident success, to de-risk the company by broadening revenue streams so that biologicals /vaccines, alongside small molecule,s have become important drivers of company sales. This strategy in no way diminishes the role of small molecules or the chemists that invent and develop them; it is not a zero-sum game. GSK, like its competitors in the sector, has not been immune to the tough environment that the industry has found itself in over the past decade. That said, quantity does not necessarily equate to quality. Even if the overall number of chemists has decreased, the quality and productivity certainly have not. GSK is undeniably endowed with a best-of-breed team of chemists so it is understandably keen to motivate, develop and retain them. These are exciting times at GSK generally where, after a period of change and uncertainty, the overall management strategy is really starting to pay dividends. Despite what a few embittered former employees might say, the company has finally got its mojo back!

    1. Dr. Zoidberg says:

      Nice try changing your username Agilist. Ironically, you attempt to blame embittered former employees for stirring up bad reputation for the company, but your constant attempts to defend corporate GSK at the first mention of anything negative really shows how embittered and thin-skinned the management there is. It’s beyond pathetic now, it’s like watching a movie that’s so bad it’s good. Just change your username to Sharknado.

    2. Anon says:

      Perhaps if GSK actually produced any new drugs rather than lots of “embittered former employees”, then GSK might deserve a bit more respect?

    3. Anon says:

      This management team at GSK has made some amazingly crappy decisions and deserves to be fired. This is the group that purchased Sirtris (-$1B) after their own internal diligence team told them not to; exited PCSK9 (-$1B per year, we know now); exited anti-thrombotics (also likely -$1B per year); greenlighted darapladib (-$1B). Now they have exited oncology. Let’s see how that one works out.

  13. TeamDabrafenib says:

    “Investing in chemistry talent is an important part of our strategy to reduce the high levels of drug discovery attrition which have been so problematical within our industry.”
    I swear this is the exact same comment that was in the “ask the CEO” section when they were laying off us rtp oncology chemists for being too successful. If you’re going to spin BS publicly at least be original don’t rehash propaganda circa 2008. It wasn’t true then and it isn’t true now.

  14. BankruptinNC says:

    Annonie: There were plenty shenanigans with Paxil and Avandia, way before Steve Nissen of Cleveland Clinic came up with his meta-analysis. I was in the room when pio versus rosi fluid retention effects were “reframed”. Google Marty Freed and Zarifa in the NY Times to see excerpts from internal emails. Nice attempt to defend GSK (I remember Chris Viebacher, Accounting Genius drug discoverer vehemently defending Avandia) but the facts are against you. Also most of the “in-the-know” executives dumped their stock options at $59/share uncannily in the weeks and months before the Nissen meta-analysis broke. Pity the SEC was (and still remains) too busy to run a retro-analysis of that trading pattern. As for retirement savings, many of us were matched in company stock, which basically wiped out a lot of non-diversifiable portfolio holdings.

  15. aerg says:

    SmallMoleculeGuy: Great to see agilist back!

    My experience at GSK is that GSK doesn’t give a hoot about any of its chemists, and is more or less glad to see them leave whenever they do. I certainly never saw the slightest interest in developing anyone.

  16. BankruptinNC says:

    SmallMoleculeGuy: Diversifying out of small molecules into “biopharmaceuticals” increases portfolio risk, rather than reducing it. Biomolecules have infinitely more complicated probability of success calculations due to constraints and risks in stability, drug delivery issues, immunogenicity etc etc. However, the story of “biopharm” does sound so sweet at those Wall Street analyst meetings….
    Some unsolicited advice to pharma investors…if the company CEO is an economist, accountant, sales guy….wannabe UK House of Lords aspirant, hedge-fund manager, ex-McKinsey guy…store your money under the mattress. It will lose less value.

  17. TX raven says:

    A few decades ago this industry was delivering new drugs, while chemists and biologists worked together well, and respected each other for what they brought to the table. Talk to a colleague with 20+ years of experience, and they will tell you how different the environment was.
    At one point the ratio biologists/chemists started increasing, the healthy relationship between them deteriorated, and eventually medicinal chemists were thrown under the bus.
    It does not surprise me that the % of biologics is increasing among newly approved drugs, as biologists have learned to bypass their chemists counterparts with this new drug modality.
    Chemists bring more that compounds to a drug discovery organization. Too bad most pharma leaders cannot see that…

  18. CMCguy says:

    Regarding Japanese long-term planning and the 80s having dealt with Japanese companies back then it did seem their attitudes where more compatible to realistic drug development timelines than those becoming predominate at US and even EU pharma. The Japanese I interacted with expressed interest was in quality and sustainability that was better overall in the long-term than grabbing a quick buck and although definitely concerned appeared to be much less frantic when projects ran into unpredictable hurdles. I am not sure if these differences remains today (as globally patience in business is rare commodity) or even if back then was a part of a culture mask used to disguise their true disappointments however it is more comfortable working in a place or with people who did express understanding and appreciate for how long things took and the many uncertainties involved in a new drug .
    As far as Planning although agree it must be tempered by reality and not extrapolated too far ahead I have always found this Quote by Ike “Plans are worthless, but planning is everything” is a sensible view.

  19. Noni Mausa says:

    It sounds like chemists should form a central pool of professionals, like dentists, doctors, steam fitters etc, an organization to which businesses would have to apply in order to hire good research chemists … call them The Chemistry Masons, with their own secret list of Businesses We Won’t Work With.

  20. Christophe Verlinde says:

    Even the USSR worked only with FIVE-year plans.
    see: https://en.wikipedia.org/wiki/Tenth_five-year_plan_(Soviet_Union)

    1. Kaleberg says:

      China currently works with five year plans. They’ve even had some success, for example, with solar power.

  21. Anonymous says:

    I have often thought that the best way to figure out the best way to run an R&D group is to determine when you had the largest number of drug approvals from in-house development and then look back 10 – 15 years and see how your R&D was being run. This was when your R&D was most productive.

  22. Levorotatory says:

    I would like to run an experiment: outsource senior management to cheaper executives in China or India and then see how the company is doing ten years later

    1. Nick K says:

      This comment made my day!

      You can be absolutely certain that senior management is the ONLY part of a company which will never be outsourced.

  23. NMRperson says:

    OK, so medicinal chemistry has been down-sizing for 15 years. The youngest staff are now in their 40’s because there has been no needed to recruit. It seems to me that you have two choices:
    Do nothing and thus plan, by default, to exit small molecule drug discovery over the next 15-20 years.
    Look to recruit some new young chemists who you hope will take the company forward in the future.
    Clearly choice two has been selected. I assume most readers consider this the correct one?
    The next problem is how to attract the “very best” people. After all it is not as though you will be recruiting in large numbers or every year. For younger readers this was what was done in the past when the industry was growing, and succession planning could be left to take care of itself.
    Even in a tight jobs market the “very best” people tend to get multiple offers. Why would such people even be looking at pharma considering the layoffs that have been taking place at regular intervals for years? Are any of you still recommending the medicinal chemistry career path to young chemistry graduates?
    What we see in this article is a plan to put choice two into operation. Will it work or even be given time to work – who knows. What I am sure of is that some credit must be due for not just settling for option 1.

  24. Neil Mathews says:

    “Head of Respiratory Therapy Area and GSK’s Chief Chemist”

    Chief Chemist?! Keep thinking up new titles, and keep reprinting the name boards on offices….

  25. Me says:

    As somebody who was hired by GSK during what was highly likely the very last milkround recruitment performed in the UK I agree more with the cynicism in the replies than in anything written in the article. Made redundant the day our department launched a new drug; colleagues in the US who hadn’t discovered anything in 35 years still in their jobs; biologists being awarded for discovering said drug, while the chemists who appeared on the patent got nothing.

    Not a chemist any more, and I am:-

    -happier
    -richer
    -less likely to take the level of bullsh*t I put up with in med chem roles
    -beginning to be convinced that contemporary molecule-metric med-chem was beginning to turn into a cargo-cult with Lipinski as it’s patriarch

    1. Peter Kenny says:

      Perhaps I should have titled the blog post that I’ve linked as the URL for this comment, “The Autumn Of The Patriarch”?

  26. steve says:

    I’m surprised that good chemists who leave pharma don’t do the most obvious thing – start your own company. The lifeblood of pharma is now in small companies. Instead of whining, take a risk and become entrepreneurs. Or, if that’s not your mindset, hook up with someone who is an entrepreneur. There’s a big world out there. There’s a huge opportunity for some smart chemists to join the cancer immunotherapy revolution – figure out drugs that block Tregs, MDSC, Bregs and other immune suppressing cell types and/or drugs that switch M2 macrophages to M1, etc. Be creative. Take a risk. Hook up with a biologist and run a company the way it should be run.

    1. Ed says:

      Steve, that sounds great in theory but with medchem you probably need to hit your mid-thirties before you come close to any degree of mastery – and by that time, probably have financial and personal commitments that make entrepreneurship hard, if not almost impossible. I know this from experience, where I had a really promising project but was working with people on the other side of the world (literally).

      1. steve says:

        Hardly anyone in biotech becomes an entrepreneur before they’re in their 30’s or 40’s; it’s not like IT where you can start young. It’s scary, I know – I took the plunge and the stress is high. But once you’ve done it you wonder why you ever thought being just another cog in a wheel was a life worth living.

        1. Hap says:

          Most people don’t want to be entrepreneurs, let alone people who have spent years being (mostly) trained in an environment that is not exactly similar to the environment of running a company (that either selects them out or requires the rarer set of people having traits consistent with both environments).

          If people start a family assuming they’re going to be around for it, starting a business is probably not compatible (as from C+E News, “And even being your own boss doesn’t always help. Philip Swain, a patent and trademark agent and the owner of IPSIS Inc., says, ‘As an entrepreneur and business owner there is little work-life balance. I foster work-life ­integration.’ “). Starting a business is likely to be as you described for some people but not for most, and it’s probably not what they were prepared for (or are being prepared for – hence the frustration).

          1. steve says:

            Then don’t complain about the big bad pharma employers. Take the bull by the horns or risk getting gored.

          2. Doc says:

            Steve, would you loan me $250m while I get started? Thanks

          3. steve says:

            Watch out for those hoofbeats behind you Doc. If you need $250MM before you’ll try to change your life then I’m afraid you’re stuck with it.

        2. Anon says:

          Good idea in theory… but difficult in practice. I’m a 15-year medicinal chemistry veteran and I looked into starting a discovery organization in the US in early 2016. It was very difficult to find money and interest. Most VC’s and Angels have shorter timelines for exits than are typically allowed by true discovery programs. They’re much more interested in clinical assets with a clear 1-3 year exit strategy. Their investment expectations have been reshaped by the recent tech boom (substantially lower operating overhead and shorter exit timelines in tech than biotech).

  27. chronicsomething says:

    Incredible to be in a room (of sorts) with so many chemists. Long story how I got here, but I have RSD in my spine and all 4 limbs (even longer story). Any idea when I might get a drug or two (not the 5 that I take now which are worthless for what it’s worth) that will enable me to walk without feeling like I’m on fire, the wind is out to get me, or I am getting stung by 30 really pissed off hornets all at once? I have to be honest, waiting for somebody to come up with something is a really hard thing to do. 401Ks and CEO windfalls all sound nice….I’d like to be able to walk past 2pm every day. If I had more than the gift of gab, perhaps esp….I’d have become my own chemist years back, before the RSD and all, ya’ll.

    1. Me says:

      There are a few trials involving anti TNF treatments for RSD. You could try to get yourself enrolled.

      So much unmet need in pain – I wonder if a tissue engineered product will come about quicker than a small molecule.

  28. chronicsomething says:

    Interesting that my attempts at researching inflammation got me here in the first place. I get conflicting information as to whether taking oral serrapeptase, for example, can work, since it wont pass thru blood brain barrier if ingested. Other than raw diets with no red meat, any other suggestions for meaningful ways to immediately go about reducing inflammation?

    1. Me says:

      It’s an enzyme, which is a protein. high school science tells you they are broken down in the stomach. Better off buying snake oil.

    2. Druid says:

      Some proteolytic enzymes are quite tough (so they don’t digest themselves when in concentrated form), so it might survive some digesting enzymes. However with a molecular weight around 50kDa, I would be very surprised if a functional quantity could be absorbed into the bloodstream and probably none at all. Some peptides can get into the gut-associated lymphoid tissue though mostly after partial digestion – this is how oral vaccines work. So for one thing, functional serrapeptase will not get to your insides.
      Then, how would a proteolytic enzyme work? It is not obvious and the promoters of serrapeptase do not offer a mechanism. Finally, where there have been large controlled clinical trials, it was not better than placebo. The only good news is that it will probably not do you any harm other than the cost.

  29. TX Raven says:

    At the end of the day, the drug discovery industry is disregarding the contributions of a motivated, talented and experienced sizable group of colleagues, who provide a unique perspective (at the molecular level) without which success is much less likely and more random.
    Any surprises progress is so slow?

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