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Drug Development

On Jadedness

It’s a Friday in midsummer, so I assume that a fair percentage of the readership is not even around! So I’m not going to do a huge detailed blog post (got one of those coming on Monday, actually). Today I just wanted to go on a bit about a problem that comes with experience in this business, thoughts brought on by some of my own recent day-job work.

It’s very hard at times to walk the line between “experienced” and “jaded”, and I think that that’s because “jaded” is the low-energy state. As everyone who does drug discovery knows, we mostly see projects fail, so psychologically, it’s beneficial not to get too attached to any one idea/molecule/project before it’s cleared some hurdles. The key is to be able to do that in a “Well, let’s see if it works” way and not in a “Yeah, that’s gonna fail” way.

I’ve recently seen some chemical matter, which is reported as binding an interesting target, that I find (gotta be honest) quite ugly. It would be easy to dismiss it out of hand, because I have never seen any compounds that look like that turn out to be useful, but that would also be irresponsible. And yes, this is all the way up to things like rhodanines and other PAINs. My take on those has always been “If you have something better-looking to work on, you’re probably better off working on that”, but for some targets, there is nothing better-looking. So the attitude (in my opinion) has to be “Compounds like this have a poor track record, and need to be approached with caution. But this is what we’ve got. Let’s put this one through the relevant assays – both the project-related ones and the warning-this-is-junk ones – as soon as we can so we can make a call”.

I’ve long tried to approach this problem in that fashion. So far, I have to say, none of the suspicious-looking compounds I’ve put to the test have made the cut. Many of them turned out to be aggregators, redox cyclers, fluorescent interference compounds – all the other classic ways to get false positives. And in a couple of cases, more tractable and potent chemical matter came along to make the issue more moot. But there’s always the possibility that one of these will be real, and the whole drug discovery enterprise makes its living on long shots.

The jadedness problem, of course, extends to more than just chemical matter. After a while, you’ve seen a lot of assays, a lot of instruments, a lot of project ideas and approaches. And since we all see a lot more negative data (and negative results) than positive, the same mental battle has to be fought. To a very good approximation, nothing in drug discovery actually works, if by “works”, you mean “delivers an actual drug”. But if you round off and make that approximation, you’re done.

Is there a limit? Yes, indeed. I draw the line at Huge HR Initiatives That Will Totally Change the Way We Do Business. I am, in fact, willing to stipulate that none of those will in fact change the way we do business. Come to think of it, everything I’ve encountered that actually has totally changed the way that any particular organization did business did so via things like 7:30 AM mandatory site meetings, people arriving at the door holding stacks of folding cardboard boxes, and presentations from HR with an entirely different tone to them. So there’s that!

46 comments on “On Jadedness”

  1. John Wayne says:

    I have a hypothesis that is is hard to gain experience in a field without also gaining a set of detrimental baggage that is a result of your negative experiences. In science, there are a lot of less enjoyable results that can negatively impact your objectivity.

    When it comes to judging the quality of lead structures, I call it ‘molecular stereotyping.’ If something burned you in the past (certain functional groups, etc.), you have a very human psychological aversion to it going forward.

    Most of us have the same thing with reactions; for example, I certainly have my favorite oxidations. I also have a second list of oxidizing reagents that reside in my personal penalty box, to be explored only when nothing else works.

  2. Isidore says:

    Actually the jaded approach usually sounds less like “Yeah, that’s gonna fail” and more like “Yeah, that’s gonna work!”, the latter accompanied by a rolling of the eyes.

  3. Nate says:

    As a corollary, as someone who has worked on a compound that is FAR outside Rule of Five space that is now being sold to patients, I find it much easier to tread on the “skeptical but optimistic” side of the line compared to those unlucky enough to have never seen their project go all the way. Being human, our experiences have a large effect on our attitude.

  4. Project Osprey says:

    I’ve always thought of chemistry as an almost schizophrenic profession. Most of our experiments don’t really give the result we want, yet we always expect our latest idea to fix the problem. It’s almost Zen in a way:

    In order to succeed you must notice trends in everything, except your own ability to notice trends.

  5. luysii says:

    The same thing happens in medicine. There are always new (and bizarre) therapies (eye movement therapy for schizophrenia and any other psychiatric problem comes to mind) for disorders with inadequate treatment. One such came out for migraine when I was just starting out in clinical practice. I asked an older GP about his experience with it — his reply –“use it while it works, Luysii, use it while it works”.

  6. respsci says:

    My jadedness usually stems from having to witness the same mistakes being made over again and again. I wish that the team, department or company, would learn from mistakes made and try to do things differently in the future. Instead, I often see decisions made along certain tracks where to me it is obvious that failure looms in the future. As a scientist, I accept that failure is the norm over success, I just wish I could be allowed to make different mistakes where I could learn something new.

    For that last point, a colleague of mine said her PhD supervisor told her that science is made up of bad years and good moments. It is those moments that make it all worthwhile.

    1. SedatedFMS says:

      This so many times over. I’ve been told I’m cynical, that I don’t have positive/can do attitude. I’m not that cynical and I’m most definitely not a negative individual. However time after time after time I see the same people, making the same mistakes, with the same results yet they end up being rewarded because they talk a good game. These people are never wrong, even when they are very much incorrect. So frustrating when style over susbtance is rewarded. And of course when you speak up………you’re labelled cynical, disruptive and negative. That is what creates jaded scientists and associates.

  7. Chrispy says:

    My experience has been that scientists, particularly in drug discovery, have nearly endless patience when it comes to things failing scientifically; I’d in fact say that they usually have too much optimism given how frequently things fail. What really makes people jaded is the HR reorganization nonsense, the Six Sigma type initiatives, employee ranking by absurd metrics like number of compounds made, an organizational lack of focus that leaves efforts dissipated over too many projects, open office plans, employment instability, unrealistic productivity expectations, new corporate slogans that are supposed to change things, and the fact that the ninnies in upper management get paid so much for so little. The science is hard enough, but the business of science can drive one over time to become disillusioned.

    1. Nick K says:

      Well said. My experience too.

    2. achemist says:

      come on, the ranking employees according to compounds made atleast gives every chemist excellent training in how to run amide couplings and suzukis

      1. SedatedFMS says:

        reaction optimisation studies, in most cases you don’t even need to work up a reaction!!

    3. Dr. Manhattan says:

      Makes you wonder what they rank the HR types on? Number of ulcers generated by ” Initiatives That Will Totally Change the Way We Do Business”?

      1. Scott says:

        Things like “reduction in employee turnover,” usually.

        “Reduction in Hostile Work Environment lawsuits” is a much harder thing to measure, and honestly usually comes down to getting enough data on perpetrators to fire them with cause.

        Otherwise, well, finding ways to save money.

        And yes, I have a BBA in HR.

  8. Joe Q. says:

    Realism is healthy and useful, but it has to be applied in moderation.

    In my own experience, “we already tried that approach and it didn’t work” dismissals from company veterans often (certainly not always) turn out to be mis-remembered in some way. The “it didn’t work” part is usually accurate, but details of what was actually tried, and how seriously it was tried, get fuzzy over time.

    1. Derek Lowe says:

      That’s a really good point. I’ve seen that as well – hindsight often makes the earlier efforts seem more comprehensive and well-thought-out than they really turn out have been.

    2. weilawei says:

      I work in a different industry, but still experience the same problem. Just yesterday, a co-worker wanted to revisit an idea that months ago I’d looked into. We just don’t have the right equipment to do it. The equipment is on order, but they didn’t want to wait for it, so we came up with a way to half-ass it to Technically Correct with a seriously large helping of Not Actually What The Customer Wants. Thankfully, our boss shot it down.

  9. nsgeek says:

    Experience in industry left me jaded in another way. I saw too many research decisions made for reasons completely unrelated to the science at hand. Projects with political momentum moving forward despite bad (or lacking) data; projects with insufficient interest from management getting starved for resource, despite scientific support and good data. Project managers and teams would often narrowly view success as ‘achieving’ milestones, whereas making solid and timely decisions to stop dedicating resource to projects that didn’t look promising was viewed as failure.

  10. AQR says:

    I think that being jaded about one’s approach to research is based on not being scientific. I have seen many medicinal chemists describe an experiment “working” or “not working” based on whether a given structural change gave a compound with improved performance.

    For example, someone will say, “I put a methyl group at the ortho position and it decreased affinity rather than increasing it so that didn’t work.” They make a bunch of other structural changes and continue to find compounds with lower affinity and they then throw up their hands and say it’s a bad lead, let’s work on something else.

    Medicinal chemists should think of the compounds they make as individual experiments. They should hypothesize how the lead compound interacts with the target and then propose compounds that modify that interaction (such as change the conformation, change steric interactions, remove or add hydrogen bonding groups, etc.) Once they have made and tested the compound, they are then in a position to draw a conclusion from the experiment. The experiment “worked” if they were actually able to make the compound and accurately determine its activity, regardless of whether the compound actually improved the activity.

    This application of the scientific method leads to knowledge about the interaction of the ligand with the target, regardless of whether the activity increased or decreased. In fact, I would argue that one gets a lot more information about that interaction from a compound that demonstrates a dramatic decrease in activity than one that has a two-fold increase in activity. If you do enough of these iterative cycles, you can learn a lot about the interaction and you can use that knowledge to rationally design compounds with improved activity.

    If you are taking a scientific approach, you are always learning something about your project and, unless you really aren’t all that interested in science, that should keep you from becoming jaded.

    1. AR says:

      Are you a practicing medicinal chemist?

      1. AQR says:

        30 plus years. Nothing on the market, but one compound in Phase 3 and another in Phase 2.

  11. BigSky says:

    My personal philosophy has evolved to “Fail with style”. If we’re gonna work on this, let’s set it up so that our results are as unambiguous as possible and we try and roll as many known knowns into the work as we can think of. All the better to be able to discuss (defend) our results later when things didn’t work like we had hoped. At least we did it correctly to the best of our imaginations.
    As an aside, but certainly a leading contributor to the “Jadeness Quotient”, the other thing that came to mind was being involved in projects where everything rolled downhill from the approach to the reagents to the xxx… everything being delineated by the Smartest Person In The Room from their perch on the carpet side of the building. Based on my self-reinforcing memory of past projects, results were always better by taking the Agile-ish approach rather than the Waterfall approach. Having more eyeballs and brainpower sitting at the decision table has never hurt me or my projects.

  12. J. Peterson says:

    Having read this blog for a few years, I’ll never understand how you (meaning the collective drug-discovery scientists “you”) get out of bed in the morning. Sure, in my non-drug related career I’ve had a few projects here and there get scrapped. But the bulk of my work over the years had made it one way or another into the hands of paying customers.

    I can’t understand spending decades of a career without a single result making it out the door and onto the shelf…

    1. John Wayne says:

      So … what do you do, and are you hiring? 🙂

    2. Dr. Victor Frankenstein says:

      It’s the small successes that keep experimental scientists going.

    3. Anonymous Researcher snaw says:

      I’m unusually fortunate because several molecules on which I have worked are being sold to patients. In each case there were (1) lots of other molecules going after the same target that went down in flames and (2) moments when we thought we’d NEVER find a compound that met all the go/no-go criteria.

      I’ve also seen several Billion-dollar-plus late stage failures. The day when your employer announces a major clinical failure are not good days.

    4. loupgarous says:

      It’s like panning for gold – now, the “pans” are so large and connected to such heavy machinery that even though the gold would slip by a prospector wading in a stream looking for “color”, the process is worth doing because even with a high failure rate (tailings versus gold), it still pays to do it.

      In med-chem as I understand it, you work with validated procedures and rational goals, and the resulting payback is so lucrative it makes sense even when most drug candidates fall by the wayside during testing.

      Something like Samuel C. Floreman’s “The Existential Pleasures of Engineering” seems to me to be main tonic for jaded-ness in med-chem. You do the work as well as you can do it, remain vigilant for ways to do it better, knowing that you, personally, may not have stellar results under your name in a paper or notes in a workbook – but that the work must be done for anything at all to be accomplished.

      1. Design Monkey says:

        Actually that large machinery currently is shaking, breaking up and grinding down and is running mostly on inertia. Financial, operational and organizational methods of earlier times there do not work anymore.

  13. Thomas McEntee says:

    I had a General Manager at the plant who told me one day after I complained about something, “I pay you to put up with the crap we deal with in this business, not for the fun you have doing your job”

  14. Barry says:

    Shoichet didn’t say “don’t assay these cmpds” or “discard assay hits with these structures”. He advised that you ask whether those cmpds still hit when you re-assay in the presence of a surfactant.

  15. CCE says:

    “Ever tried. Ever failed. No matter. Try again. Fail again. Fail better.” -Beckett
    We’re in the business of failing better, I remind myself when feeling jaded.

  16. Dr. Victor Frankenstein says:

    As jaded scientists, we are actually surprised if something actually works as expected.
    We may even be suspicious of a positive result and expect it to be a fluke!

  17. Kling says:

    Erooms law suggests the drug discovery industry will crash, due to many factors mentioned in this post. The desperation spawns business and political decisions to game a biological system we barely understand.

    1. loupgarous says:

      I keep thinking of how self-driving cars finally happened (or are about the happen realistically). The US Air Force funded the first serious candidate for the genus that didn’t require an instrumented road (God’s Own Slot Car Track), a Chevrolet Step-Van loaded with a mini-mainframe computer and various sensors. Before and after that point, the Department of Defense paid for Big Research to solve the problem.

      But until DARPA’s first series of Grand Challenges, progress toward autonomous road vehicles was glacial. For a cash prize which was a fraction of the cost of any of the prior research funded by DoD, volunteers placed their free time, their own money, and vehicles (some probably donated by courageous car dealers) at risk to achieve great things. And so they have.

      At the risk of having an entire comment space full of People Who Do It For a Living eviscerate me verbally, is it time yet for DARPA Grand Challenges in Clinical Research and Drug Discovery?

      The goal would be development of more rapid and economical drug discovery, development and clinical trials than we now have, with the same or better safety margins for patients and safety volunteers. I’m sure not suggesting you all aren’t far more diligent and competent at what you do then I was as a clinical data analyst. I’m just wondering if it’s not time for DARPA or a Dr. Diamandis to dangle large cash prizes and fame before those who might make better tools for a more efficient and less expensive pharmaceutical research and development industry.

      1. Design Monkey says:

        loupie, first, history, technology and problems of autonomous cars are way more rich and complex than you are trying to primitivize.
        Second, read https://doi.org/10.3109/14756366.2015.1021252 and then tell how would you grand darpized it, as not to come to the state it is now?
        Third, suppose one has cardiovascular (or even Alzheimer’s) prophylactic drug candidate. How the hell would you propse to demonstrate their efficiency without large, long and helluva expensive clinical trials?

        1. loupgarous says:

          I’ve taken part in trials at all levels, from patient, to statistician at clinic level (at that level “statistician” is more to do with collecting data than analyzing it), to medical writer, to clinical data analyst (writing software to evaluate drug safety and efficacy). I know a little about the cash burn in large multicenter studies (at the multinational Big Pharma outfit where I last worked, the average expenditure for New Drug Approval-related data work was about $300,000/day (and some NDA projects ran a year and a half), and that was in the 1990s. I’m sure it’s much higher than that now. That’s neglecting pilot plants, legal hire, et cetera.

          How to get the price down? I can only speak to what I know. Most clinical research data are compiled with custom programs written in SAS or Oracle, and SAS System dominates the market. Part of why it does is that clinical research data collection was, when I worked in the field, tied to old computing hardware (IBM System 70, VAX, that kind of old).

          Much time and labor is spent migrating and transforming clinical data from Clinical Research Forms (usually hand-entered from patient charts) to PCs belonging to a clinical research organization (each CRF entered at least twice to screen for errors in data entry), then entered into a database, which is analyzed with small custom-written programs in SAS according to a study design developed by one or more statisticians.

          At the Big Pharma outfit where I helped do safety and efficacy on a recombinant insulin analog, we had a team of Chinese stats guys designing analysis methods at a relatively low level, and a Russian emigre overseeing their work and applying Bayesian methods to the data they developed, so we programmers could hand-craft SAS code to plow through the CRF databases and turn the numbers into reliable reports on drug safety and efficacy.

          I’d be willing to bet that much of that has not changed since I left Big Pharma. It could change, but someone needs to stand from the outside and look at how much money it costs to analyze clinical research data the way we’ve always done it. The firm I last worked at probably amortized the IBM mainframe they maintained their clinical databases decades before I worked there. Costs of data transformation and wild inefficiencies in that process (requiring large staffs of clinical data professionals) are a large part of why clinical research is so expensive. It could be much less expensive and faster at the same time.

      2. Kaleberg says:

        DARPA works by funding projects to build the necessary research and development infrastructure. They build labs, train researchers, fund research and pay for the development of new toys. They have a 30-50 year horizon. By the time of DARPA’s big desert challenge, there were universities cranking out the appropriately trained PhDs, research labs full of promising research, companies selling improved sensors, faster computers, improved algorithms and better actuators. The automotive industry had moved to drive by wire. Companies couldn’t built that kind of infrastructure. A ten year horizon is an eternity to a corporate entity.

        P.S. Self driving cars are much farther from successful implementation than the hype would indicate. My guess is that we will see them in use over the next decade, but the door to door fantasy will remain a fantasy.

  18. Anonymous says:

    (Off topic: (1) There are times when I wish that Pipeline was built on real forum software instead of blogging software. It would be easier to follow sub-threads with short replies to specific posts instead of my long composites. AND, I’d often like to give likes or dislikes to specific replies. But then it’s a Forum, not Derek’s Blog. (2) There are times when I wish that there was an embedded structure drawing applet (there are some free ones) on the site and a way for respondents to include an explanatory structure or two, especially for the non-chemists who don’t know what the chemists are talking about.)

    This is another time I wanted to give a “like” to a post by luysii. “I asked an older GP about his experience with it — his reply –“use it while it works, Luysii, use it while it works”.” 🙂 “I asked the Director about the garbage coming out of the combi-chem stuff and his reply was ‘use it while it works, Anonymous, use it while it works.’ ” (In truth, the Director said it was great and going to transform drug discovery and we’d make lots of new drugs.” Pffft.) And the list goes on.

    A “like” to SedatedFMS for “And of course when you speak up………you’re labelled cynical, disruptive and negative.”

    “Like”s for some others, too.

    I have been fully on-board many projects but not blindly so. From my earliest (undergrad) training, I was taught to question data. I am eager to take calculated risks based on good precedents — or even BAD precedents! — and good planning. I do not become disillusioned when projects fail (“normal science” – you still learn something). However, when those failures are misrepresented and published (“abnormal science”) and used to promote the careers of others, I suppose that I sound more jaded.

    Why do I have an overwhelming urge to want to post links to several hundred Dilbert cartoons? July 11:
    Pointy-haired Boss: “Everyone says you hate the new product test plan.”
    Dilbert: “No, I like it.”
    PHB: “Pfft. I don’t think all of those people can be wrong about what you think.”
    D: “I’m kind of an expert on what I think.”
    PHB: “I guess it’s just your word against everyone.”
    (There are much better ones, of course, but too wordy to type.)

  19. Anon says:

    I wish the old jaded folks would stay away from evaluating the ideas and proposals of younger, more enthusiastic folks.

    There’s nothing that pisses me off more than feedback like “too risky, probably won’t work”, “similar ideas have been tried and failed before” and my favourite, “need to see more proof/evidence that it will work before testing whether it will work”.

    Firstly, an idea is *not* risky if the cost of failure is small, no matter how likely it may be to fail. The real risk is in not trying any bold ideas and following the status quo path to irrelevance.

    Second, the fact that similar ideas have been tried before is a good thing, as it confirms a real need/problem that needs to be solved. There are too many “solutions” looking for non-existent problems.

    Third, the fact that similar ideas have failed before is also a good thing, because they are not exactly the same, and if they had worked there would little reason to try something a bit different.

    And finally, the notion that somebody needs more evidence that an idea will work before testing whether it works, just means they do not have the entrepreneurial mindset of an innovator. These folks will kill any hope of innovation and should either step out of the way, or get fired. They are a complete waste of space.

    1. Anonymous says:

      “I wish the old jaded folks would stay away from evaluating the ideas and proposals of younger, more enthusiastic folks.” Emphasis: JADED. Contrast that with “experienced and knowledgeable.” When I first read about Theranos, probably a couple of years into their venture, I was intrigued. I did some simple calculations on the amounts of a few common analytes in one drop of blood and they were far below the detection limits of state of the art instruments that I knew about. I wondered, “How are they going to deliver on their promise?” (Some analytes can be amplified biologically but others can not.) I was now a skeptic but I wanted to see what breakthroughs they had achieved, either in biology (amplification) or instruments (sensitivity). $900 M later, they had NOTHING other than criminal indictments and convictions. I have heard of smaller ventures, built on ENTHUSIASTIC promises with false claims that sank into obscurity taking only tens of millions of investment dollars with them each time – not worth a headline.

      “There’s nothing that pisses me off more than feedback like “too risky, probably won’t work”, “similar ideas have been tried and failed before” …” How about, “Based on these precedents, that is somewhat risky (without the superlative)” and “These prior efforts have failed. Why did they fail and how is this approach different?” and so on. “Enthusiasm” alone doesn’t cut it, at least not with me.

      “an idea is *not* risky if the cost of failure is small, … ” EVERYONE does their own version of cost-benefit analysis when evaluating a project. Experience and knowledge provide a more accurate estimate of both. A “simple” experiment in the lab can actually be very costly to execute, as known to those who DO it. Scale that up into large scale research investment HONESTLY. But it is also the case that very few investors are interested in small, low risk investments. VCs won’t look at promising, low risk projects that are too small. They don’t want to put in 1 to make 10. They want to put in 10 M to make 100 M.

      “The real risk is in not trying any bold ideas …” I have heard some extraordinarily brilliant, low risk (favorable cost-benefit ratio) ideas over the years. FA Cotton had an essay in C&EN before he died lamenting that academia is NOT hiring the best, most creative scientists but only those who were fundable. At that time, he lamented that TAMU was only making offers to those who had a dendrimer or buckyball proposal. “Bold” to me is not the same as “bold” to you, the NIH/NSF, DARPA, or VCs.

      A previous Pipeline topic mentioned that there are over 200 new ventures pursuing AI for clinical medicine and healthcare, almost all of them comparable, in some way, to IBM’s Watson. I heard a YOUTHFUL, ENTHUSIASTIC pitch for yet another such company. I asked where they would get the data to power their app. THEY HAD NO IDEA that the underlying data is proprietary and costly. VC mentality is sometimes that “If the competition is funding it, we’d better invest, too. Quick! Find me an AI Med company to invest in!” That youthful, enthusiastic innovator has a good chance of getting funding with a spiffy slide deck to back him up.

      “the fact that similar ideas have been tried before is a good thing …” True. So learn from them, don’t ignore them or sweep them under the rug. Or, in many cases, SELECTIVELY ignore the previous efforts that undermine the novelty of the new, but ENTHUSIASTICALLY promoted, ideas.

      “the fact that similar ideas have failed before … try something a bit different.” It has been posted in Pipeline many times, that a lot of new stuff isn’t so new. Verge’s Zhang is going to combine AI, genomics and wet lab to transform drug disco!! Verge says, “The problem is finding the right target!” Just one example, Millenium Pharm was founded on the promise of exploiting genomics and AI and wet lab to produce drugs. I think their first drug was an already approved drug they licensed to sell in the US from a Japanese company. Their next success was Velcade, a “traditional” med chem discovery (brought in in-progress when they acquired another company; some versions of the story are that management tried to kill the project). Modern AI is more powerful; genomics is cheaper and better; what is Verge’s differentiator? ENTHUSIASM!! They’ve got enthusiasm!

      “the notion that somebody needs more evidence that an idea will work before testing whether it …” Have you ever dealt with VCs? VC has gone through stages. For the past decade (or more), many VCs gave up on new ventures and only wanted late stage — lots of proof — investments. One example comes to mind: abiraterone was developed and advanced, mostly in the UK. The company was struggling and on the brink. VCs swooped in and bought the company and the US FDA approved abiraterone very soon after. That was a HUGE payday for the VCs.

    2. Design Monkey says:

      Anon, as Niels Bohrs said: An expert is a man, who has made all the mistakes which can be made, in a narrow field.

      Your young, bold and enthusiastic one still has that ahead of him. And then there is also a category of young, bold and enthusiastic elizabeths holmes.

    3. Design Monkey says:

      Anon said: they do not have the entrepreneurial mindset of an innovator.

      Anon, as far you are enterpreneurially innovating on your own personal cash funding, you are free to innovate whatever you want (provided your innvations are compatible with criminal and other laws).

      If you are trying to do it on other peoples money, then those other people will evaluate your enthusiastic ideas (and perhaps will not find them as grand as you yourself think). That’s how the word is built, anon, if you have not noticed before.

    4. Lambchops says:

      @ Design Monkey

      Or indeed the Arthur C Clarke quote that

      “When a distinguished but elderly scientist states that something is possible, he is almost certainly right. When he states that something is impossible, he is very probably wrong.”

      I seem to recall seeing a talk where an academic involved in early DPP-IV inhibitor research recalled challenging such a scientist before later on adding a mea culpa that he subsequently became that scientist itself when dismissing the chances of success for SGLT-2 inhibitors.

      1. Design Monkey says:

        lambie, you did not get it. Again, for slow ones: as far you are enthysiastically innovating on your own cash funding, you are free to do whatever you want. No elderly distinguished scientists can forbid you anything.
        However, if you are trying to mooch money from other people, then situation happens to be different.

      2. Design Monkey says:

        Regarding recallings: 10 years or so ago there was irish company Steorn, who boldly innovatively promised perpetuum mobile, to charge mobile phones, to pump water for poor natives in Africa and what not else. Elderly distinguished scientists (and any competent person) dismissed them as fraud.

        And surprise, surprise – they were right, that Steorn company indeed was fraud.

        Still is. It seems that they still are screwing especially stupid lambs on money selling them perpetual motion phone chargers for 1200$. (Wonderful laws in that Ireland. holmes chick’s biggest error of life was that she did not founded her theranos thingy in Ireland)

        “There’s a sucker born every minute.” ―attributed to P.T. Barnum

    5. Somhairle MacCormick says:

      I always tried my ideas in the lab, then asked my boss what he thought of them. So when someone suggests something to me now I say give it a try. Unless it’s clearly crap.

  20. Anonymous says:

    Having tons of old inactive 6-figure-a-year tenured deadwood faculty to the left of me, and legions of cheap chinese-national labor to the right makes me incredibly jaded about academic science. WTF?

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