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End of a Year

This is my last workday of the year – I’ll be posting occasionally into the new year, but some of those will be recipes (as is traditional around here). If there’s any big scientific news, though, I’ll rouse myself and talk about it. Today I’m just heading into the lab to get things wrapped up, leave a few slow reactions sitting over the break, and leave myself notes about what I’m doing when I get back.

I’ve been trying to take my own advice this year and work on some hard problems, not that we necessarily have a lot of trivial ones in drug discovery. Even when I’m working on something that’s not up there at the edge, I try to keep my eyes open for results or ideas that might be relevant to bigger issues. That’s always the balance in doing scientific research – you have to keep your head down and pay attention to details, because they’re important, but you also have to look up and see where you are in the broader landscape, because that’s important, too. This year’s work, overall, has been good; I hope to have some publications on some of it to show what’s been going on. Overall, I’m sticking with the recommendation to work (when possible) on the hardest, most important problems available. I’ve always preferred projects that are in this category, anyway, for purely pragmatic reasons.

In drug research, when you work on something that everyone thinks is a sure thing, it’s nothing of the sort. We don’t have sure things. The projects that are seen as more “out there” are (in reality) not that much harder, if at all, than the ones that people are already mentally putting in the “bound to work” category. And when one of the so-called long shots actually works, everyone who helped it gets a share of glory, whereas if the sure thing delivers, well, not so much. It was going to work anyway, right? No matter who was on it? The only thing the can’t-miss project can do to surprise anyone is to miss, which it already has a better chance of doing than people are giving it credit for, and when it does wipe out, someone obviously has to be blamed. It was a sure thing! How could you have messed it up?

So I have a lot more sympathy for long-shot projects, and less trepidation about working on them. Everything’s a long shot – look at how many drugs actually get through. I look forward to another year of oddities, surprises, reversals (in both directions) and sudden insights (a few more of the latter would not come amiss). You probably know Isaac Asimov’s line about how the real sound of a scientific breakthrough isn’t a shout of “Eureka!” It’s someone, he said, looking down at a flask or printout and saying “Huh. That’s funny”. And he was right, although the downside is that we do a lot of that when it turns out not to be any kind of breakthrough at all. But I’d far rather have those moments than not. As I was telling some folks the other day, I’m pretty well ruined, by this point, for any job where I would know what was going to happen.

Bring on another year, then. I can’t fix the world or what’s wrong with it, but if things go well I can figure some things out that no one has figured out before. May our hypotheses turn out correct once in a while, may our error bars be small, and may our experiments reproduce and the stakes be as high as we can make them when they do.

41 comments on “End of a Year”

  1. James says:

    “May our hypotheses turn out correct once in a while, may our error bars be small, and may our experiments reproduce and the stakes be as high as we can make them when they do.”

    I am probably going to have to steal this quote when it comes to wishing other scientists around here a happy new year… Sorry.

  2. Isidore says:

    “May our hypotheses turn out correct once in a while, may our error bars be small, and may our experiments reproduce and the stakes be as high as we can make them when they do.”

    Hear, hear!

    Merry Christmas and Happy New Year, sir!

  3. bhip says:

    I would add “may your management be good scientists”….a true Christmas Miracle!!

    Hope you & your readers have a restful holiday season…

  4. NHR_GUY says:

    And may our rotovaps not bump

    BTW, there are no bump traps in heaven

    1. Mark Thorson says:

      What, you’re going to leave it running over the holidays?

    2. An Old Chemist says:

      To circumvent the problem of bumping/splashing stuff in rotary evaporators, I have lately been using ‘Splash Guard, Adapter, X-Coarse Frit’ (CG-1041-F-03). With this device, nothing ever bumps and creates a mess. This is especially helpful when my compounds are foams, solids, and aqueous buffer solutions.

      I wish you a Happy rotavopping and compound recovery in 2017!

  5. Memories says:

    I worked as a process chemist from 2009-2011 after graduating in 2008. During those years, our department always concluded work so that there were two weeks where the department wasn’t operational. Two weeks of vacation after grad school – I almost didn’t know how to enjoy so much time off guilt free. My chemical development department was shut down in 2011.

    I transitioned to medical device manufacturing – we are expanding so much and have so many orders to fill that the plant is shut down only on December 24th and 25th, and January 1st. The remainder of the holiday season has mandatory shifts to meet production and I have to schedule employees for mandatory overtime. Two weeks of vacation here is merely a dream.

    I miss process chemistry – but I don’t miss wondering if this was the year my department would be shut down.

    Happy new year to all the discovery and process chemists out there. I hope there’s some of you left by 2020. I didn’t make it – but I’m happier now.

    1. Me says:

      Lol I could have written something very similar about discovery chemistry/med chem. My billable hours targets need to be met regardless of the season, but I am happier, better paid and less concerned about future employment prospects.

  6. Curious Wavefunction says:

    At this point, I am simply content to satisfy the mandate of the Chinese adage wishing us to live in interesting times. There’s plenty of those around for sure.

    1. CMCguy says:

      CW based on certain typical associations have viewed “interesting times” more as a curse than a mandate and yes have had plenty but do wish for less often

  7. luysii says:

    It is now permitted to say Merry Christmas, Happy New year and best wishes to all. Here is a photo which should make you feel good —

    https://luysii.wordpress.com/2016/12/18/noel/

    1. Dr CNS says:

      Luysii…
      It was never forbidden, as far as i know.
      As i profess a different religion, it does bother me when someone who doesn’t know me assume i practice their own religion. It feels arrogant… Oh well, i better get used to it…

      Best wishes for everyone – and thanks Derek for giving us the chance to grow and learn.

      May your neurons synapse perfectly!

      1. luysii says:

        Dr. CNS:

        What neurons I have left appear to be working sporadically.

        If you work as a cashier, waitress, deliveryman in a business of any size, you are likely forbidden to say Merry Christmas to people you see throughout the year even though this may be your only contact with them.

        Cultural appropriation is the latest no no. Saying Happy Holidays (how incredibly insipid) is a form of cultural castration, and to me, far worse.

        1. CR says:

          And if they are not Christian? Of course we should just simply assume a nice Merry Christmas is appropriate for everyone. Only simple minded people are offended by Happy Holidays (or the arrogant). There is no “war” on Christmas as Fox (and Trump and the like) would like us to believe, there is simply a realization that not everyone recognizes Christmas and there is nothing wrong with that.

          1. Celt says:

            Simple minded people like those who do not get holidays at Christmas? I think they’ve at least as much of a beef as those who take offence to Christmas because of different religions.
            As a former pagan…I see equal reasonableness to be offended by all these people culturally appropriating our ancient tree tradition…

        2. anon says:

          I thought this angry old man finally found his piece after the election. I guess I am wrong.

          1. Bagger Vance says:

            “sharing his own beliefs in the joy of the season” = “angry old man”

            Keep up the good work, guys, you’ll bring more folks to the alt-right every day.

          2. Hap says:

            1) I get not wanting to make people unhappy, but there aren’t really any holidays which are intended by “Happy Holidays”, I think, other than Christmas. Hanukkah and Eid (I think) don’t have proportionate importance to the amount of hoopla we have, and Kwanzaa is sort of retconned (though I guess so was Christmas, once upon a time) and celebrated by a limited population. At best, “Happy Holidays” is a euphemism like “passing away” for death, but it’s not a terribly honest one.

            2) If criticizing people’s complaints about Christmas terminology (or even the perceived threat to American culture, whatever that means) turns someone into a metrosexual Neo-Nazi, then there’s really not much to say. Someone with that much hate and that little logic is not going anywhere good, fast.

          3. Bagger Vance says:

            wtf “metrosexual”? (link to better description in handle) Media aspersions aside, you will find that most of what it offers used to be considered “common sense.” I mean, if I believe in a specific holiday, why shouldn’t i express that?

            Anyway “Happy Kwanzaa” or whatever to you Hap; perhaps you will learn more about us in the Coming Year .

        3. Design Monkey says:

          One can always answer : Merry Dies Natalis Solis Invicti to you too, or pick even more interesting replies to religious propagandists.

          1. Ken says:

            “May dead Cthulhu consume your soul quickly when He wakes”, that sort of thing?

            (Actually as a Christian, I find people weaponizing “Merry Christmas” far more offensive than “Happy Holidays”.)

    2. Passerby says:

      This exchange is a good example of why this country’s going to hell in a handbasket; it’s because somewhere we have lost track of the important things and are wallowing in the trivial. People are spending more time debating about whether to wish each other Merry Christmas than fighting disease, poverty, pollution and scientific ignorance. Seriously, who cares what my neighbor wishes me or whether LGBT people use one bathroom or another! Fortunately blogs like this provide a slight glimmer of hope that all may not be lost yet, that some people at least care about things that actually matter.

      1. Dr CNS says:

        Dear Passerby,

        I hope your diagnosis about the future of the USA is incorrect.

        I think you are starting from the wrong end. In order to discover drugs we need goos teams. To have good teams we need folks that at least respect each other. Not so easy to get these days.

        Agreeing on basic things is a good way to start building a common path forward, especially one for the longer term.

        “May your tlcs be spot-to-spot”

        1. Li Zhi says:

          I really hope you have an incredibly horrible December 25th. There, is that better?

          1. Combichem says:

            See… America is already great again!
            Just wait a few weeks and see all those med chem jobs coming back from China!

    3. Kaleberg says:

      When was it forbidden to say Merry Christmas? Perhaps in February or July.

  8. Bagger Vance says:

    Thanks for an interesting year Derek (and fellow commenters) and going forward i promise not to obsess about politics here more than anyone else.

    Current year is best year. MAGA!

  9. Hap says:

    In some sense, this entire year has been a year of finding out things that you knew that weren’t true, and things that you had that you should have valued more but didn’t when you had them. Science is about pulling those sorts of veils from human experience, among other things.

    I hope that next year will either be better than this one or we will at least come to grips with the knowledge of ourselves that we’ve found.

  10. luysii says:

    Pleasantries aside, all should relax and enjoy — https://luysii.wordpress.com/2016/12/18/noel/

  11. Scott says:

    I’m rather fond of an old line from EE Smith: “May there be lots of bubbles in your think-tank”…

  12. BK says:

    I’m gonna be all hipster here and say Happy Kwanzaa instead (yes I know it’s the 26th).

  13. CR says:

    Festivus for the rest of us.

  14. SedatedFMS says:

    Bah chuffin’ humbug the lot of ye.

  15. Doug Steinman says:

    I had the honor this year of heading up a non-denominational tree lighting and peace ceremony for my local park district. As it was the first year only about 75 people showed up. However, everyone left with a good feeling and I felt a great deal of satisfaction that I was able to help give the community a lift after all the negative feelings generated by the election. I fully retired this year so no work complaints but I wish for everyone the greatest success in the new year. There remain so many critical needs for new treatments and I wish that everyone will be able to work on projects, like Derek, that are important and significant. Happy Holidays to all.

  16. dearieme says:

    Merry Christmas and a Happy New Year, Derek.
    Lang may yer lum reek.

  17. Hap says:

    Happy Holidays, Dr. Lowe. (I don’t know what else to say, comment above notwithstanding).

    I hope the new year is good.

  18. Dr Phibes says:

    “And when one of the so-called long shots actually works, everyone who helped it gets a share of glory, whereas if the sure thing delivers, well, not so much. It was going to work anyway, right?”

    I dunno. I was on a project that we *knew* worked – had done so really well in PhII and was now steaming ahead great guns in PhIII. It was a “slam dunk” as I think you Americans say, but still it was chicken on Sunday and gravy for all. I was only peripherally involved: on the team, but my contribution was close to “bugger all”, as we Brits say. Yet still I got all sorts of nice presents for my “work” on it. But it was very high profile (and ultimately successful and made lots of $$) so I suppose that were happy to spread some of the joy about.

    Anyway Happy festive Season to you, Derek. Next year in science & politics is sure to be “interesting” (as the Chinese Curse has it) and I’m looking forward to your take on it.

  19. Andy II says:

    Came across an interesting article at The Hill.

    “A woman battling leukemia sat across from me the other day, eager to hear the news:

    Would she qualify to be part of a clinical research trial? Or not?

    Her quandary is far too common. Thousands of adult cancer patients with limited available treatment options are considered for clinical trials, but fewer than five percent are actually selected.

    And that is a national disgrace. The 21st Century Cures Act, just signed into law by President Obama, supports the Vice President’s Cancer Moonshot, which identifies the low number — less than five percent — of adult patients considered eligible for cancer clinical research trials as one of the main barriers to progress in the war against cancer. Compare this to the 60 percent of pediatric cancer patients who enroll in such studies. Why don’t adults appreciate the same imperative?”

    http://thehill.com/blogs/pundits-blog/healthcare/311312-the-disgrace-of-cancer-clinical-trials

    I think it is reasonable for a sponsor to set rather strict inclusion/exclusion criteria for a registration trial. Remember the clinical study done by BMS with Opdivo?

  20. David Edwards says:

    Am I the only one here not only wishing Derek well for the season, but that he also be inspired to add yet more gems to TIWWW?

    It’s thanks to that section that I came here in the first place, then started hopping around and looking at other sections. Even though it’s a long time since I had anything to do with glassware and reagents, and chose instead the rather less tactile joys of software, I still have fond memories of my student days, which included a fair dose of chemistry, a subject I still have a lingering soft spot for. Derek reminds me why I developed that soft spot in the first place. 🙂

  21. Mark Thorson says:

    I’m still waiting for the promised recipes, but since nobody has been forthcoming I’ll give you my recipe for deep-fried wonton.

    Of course, you’ll need to buy wonton wrappers. I always get the thinnest ones available so that the crust doesn’t overshadow the ingredients, but I have the luxury of shopping at several local Asian supermarkets. Elsewhere, you may have to take what you can get.

    I start with pork sausage meat, usually the sausages from Trader Joe’s, which I squeeze to empty out the meat from the casings. I brown this in a pan, which I do in two batches so it browns instead of steaming. I drain off the fat and then wring out the meat in paper towels to get it even drier.

    I usually use chopped yellow onions, chopped red bell pepper, and chopped white button mushrooms as the additional components. The onions are for flavor, the bell pepper is for color, and the mushrooms are for texture. I usually pan fry each one separately, because they cook at different rates and I want each one to be right on the button. Onions yield a lot of water, and I don’t want that to be soaked up by the mushrooms. Very important — note that I fry all of the filling material. This is to drive the water out so the wontons don’t blow up with steam and explode or spatter when fried.

    The final step in preparing the filling is to put some soy sauce in the pan and reduce it to a syrupy consistency. At this point, all of the fried ingredients are added back to the pan and tossed in the reduced soy sauce to coat them. The amount of soy sauce to use depends on how salty you like your wontons and how much ingredients you’re using.

    Now I set aside the filling material to cool. I recommend doing all of the steps up to this point on the previous day, then refrigerating the filling overnight.

    The next day, I first assemble the wontons. The main error to avoid is overfilling the wontons. That can cause them to burst while frying. Use something like a teaspoon to meter the ingredients and make them all the same size.

    I seal the edges of the wonton wrappers by dipping a finger in a cup of water and wetting two adjacent edges roughly finger-width. (No egg white is needed.) I then fold the wrapper over and seal the flap against the wetted edges. Now you have a triangular shape with a 90 degree corner and two 45 degree corners. I wet one side of the 90 degree corner and seal it against the body of the triangle. I wet one of the 45 degree corners and seal it to the other one by wrapping these ends around my finger. The ends meet on the opposite side from where I sealed the 90 degree corner to the body.

    Assembling the wontons will take some time. I usually lay them out on brown paper grocery bags that have been cut along their seam and the bottom to make a big sheet of paper. Try to keep the wontons dry as you assemble them so they don’t stick to the paper.

    Now we fry them. Put a layer of oil in the pan which is about 2/3 the thickness of the smallest dimension of the wontons. You don’t want the oil to be so deep that the wontons are floating, otherwise they’ll rotate like an iceberg with their heavy side down. You want them to touch the bottom, so that you can control which side is down. You’ll fry them first on one side, then flip them and fry on the other side.

    On my stove, I have to fry at the maximum flame height because that’s barely hot enough to do a good job. You want them to take a few minutes to fry so you get an even browning. I once used an electric stovetop that was super hot. I started at the highest setting, and I almost caused an oil fire. The oil was shimmering and starting to smoke. The wontons were browning on one side in about 10 seconds, which is way too fast. You should keep an open box of baking soda next to the pot, so that you can dump it in if the oil catches fire. I’ve only had to do this once, and it’s really amazing how fast it snuffs the fire out. The box needs to be open before you start heating up the oil, because there won’t be time to open it after the fire starts. Also, you’ll be panicking.

    Drain the fried wontons on a wire rack. I used to drain them on paper towels like my mom did, but this tends to trap moisture near the wontons as they cool. A wire rack gives air circulation under the wontons, which helps preserve their crispiness. I used to serve them with something to dip them in, but I don’t do that anymore. Any kind of a sauce will get in the way of appreciating a good wonton filling. I’ve experimented with many fillings before — even an Italian style with pesto and Parmasan cheese. I’ve used meat artisenally smoked over my barbeque. I’ve used chicken and I’ve used shrimp. I’ve made them vegan with curried seitan. I think the pork-onion-pepper-mushroom combination is the best.

    1. Mark Thorson says:

      A note on quantity. I believe the packages of fresh pork sausages I use are 1 pound. They have five big sausages in them. I use one package of fresh white button mushrooms. I believe those are 12 oz. I slice them into pieces that are 2-3 mm in their short dimensions, longer in their axial dimension. Two red bell peppers (though one will do), cut into the same size as the mushrooms. Two medium to large yellow onions, cut down the polar dimension to make strips 2-3 inches long and 3-5 mm wide. They shrink a lot when fried. The onions are browned (caramelized), while the red bell pepper and mushrooms are just sort of browned around the edges and not browned as severely as the onions. I do the onions first, then the peppers, then the mushrooms. This is so the mushrooms pick up any residue in the pan from the other vegetables.

      When you heat up the oil, put a drop or two of water in it. The oil will be getting close to temperature when a drop makes a crackling sound. Then take a spare wonton wrapper and see how fast it browns. 90 seconds would be about right.

      I fish the fried wontons out of the oil with a giant perforated spoon. Tongs would work too, but that’s slower so you would want to run at a lower frying temperature. The Chinese use a woven brass wire basket with a bamboo handle. Those things are basically impossible to clean, so I don’t use them.

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