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Blog Housekeeping

Housekeeping

Holiday-season travel is cutting into valuable blogging time around here! I’ll see everyone on Wednesday, but of course after this week things are going to go slow-to-irregular for the rest of the year, anyway. . .

In the meantime, though, let me throw the floor open in the comments. What topics haven’t been covered around here recently that you feel should get more attention? Any stories that need revisiting in the light of more recent events? No promises, of course, but I would certainly be interested in nominations in these categories. Thanks!

68 comments on “Housekeeping”

  1. Aditya Kulkarni says:

    Hi Derek,

    Can you share your thoughts on the field of Innate Immunity modulators? Particularly the STING agonists which were all the hype but have had discouraging clinical trial results from Merck and Aduro/Novartis. More recently GSKs systemic small molecule STING agonist has also entered clinics. Would be great to hear your thoughts on this.

    Best,
    Aditya.

  2. An Old Chemist says:

    “The future of the small molecule drugs” and hence the employment of synthetic chemists in the pharma industry. On the list of the top 20 top-selling drugs of 2018 and 2019, about half are biologic drugs. Now, hopefully in the near future, gene-editing drugs (CRISPR-3), cell-based therapies (CAR-T), and personalized biological medicines will be leading the way to the disease management. Artificial intelligence and machine learning will also make a lot of scientists redundant.

    1. Waling into the horizon says:

      An Old Chemist… you bring up an excellent point, and one I wish there were more awareness of.

      With the migration of most drug discovery resources to areas with a perceived larger probability of success and financial rewards, many other therapeutic areas are being deserted. CV, metabolic disease, CNS, infectious diseases…

      As hard as all drug discovery is, the bar appears lower for oncology or rare diseases, and that’s where capital goes. I wouldn’t blame them. They exist to make money, as soon as possible, as much as possible, and not to do what benefits society in the longer term.

      Yet, we must keep an eye in the longer term and do something about it, or we may not get there. As you, I feel that we are now moving into a future with a reduced ability to discover small molecule drugs, as medicinal chemists become redundant, their perspectives are not prioritized by colleagues coming from orthogonal sciences, and eventually vanish from the life science ecosystem. I don’t think this is a welcome development, as biologics cannot address all medical needs. Especially at the current cost of the drugs being approved.

      So, should the NIH focus on funding mainly areas not prioritized by the private sector? Would this be a way to balance the short-term and long-term interests of the life science ecosystem?

  3. Mark Tuttle says:

    Why did FDA approve golodirsen after giving it a CRL? what is going on over there with respect to DMD and also just generally approving drugs with little evidence of efficacy?

    1. loupgarous says:

      Derek may have insights into that not available on the Web, but Sarepta’s press release on the matter is here, for what it’s worth.

      Sarepta acknowledges one of the CRL’s concerns, renal toxicity, noting it was seen at 10x the dosage levels used in clinical studies. They (interestingly) didn’t address the other concern raised by FDA in that CRL, the risk of infections related to intravenous infusion ports.

      So, you guys who know a lot about tox screens – a tox signal at 10 x clinical dosage is still a positive tox signal, right?

      1. Eric says:

        Yes, it is a tox signal. Remember, however, that the goal of a toxicology study is to find toxicity. The goal is not to say “it’s a perfectly clean compound” because in reality that almost never happens and if it does it would likely indicate that the administered dose was not high enough to identify the target organs.

        Based on the assumption that every drug has toxicity, the relevant question is – what is the safety margin? Is 10x enough? That’s dependent upon the disease in question and the severity of the toxicity. This is the gray area where FDA decides the risk/benefit ratio and it’s different for an acne treatment vs DMD.

    2. loupgarous says:

      @Mark Tuttle Sarepta’s press release announcing approval makes clear that this is on the FDA’s “accelerated approval pathway”,

      ” the continued approval of Vyondys 53 may be contingent on confirmation of a clinical benefit in this post-marketing confirmatory trial

      and

      “Sarepta’s placebo-controlled, post-marketing confirmatory trial to support the Vyondys 53 accelerated approval – titled ESSENCE – is currently enrolling and expected to conclude by 2024.

      .
      It’s somewhat more restrictive than a regular New Drug Approval.

      Sarepta mentioned much the same thing in their press release when they got approval to market eteplirsen:

      Under the accelerated approval provisions, the FDA is requiring Sarepta Therapeutics to conduct a clinical trial to confirm the drug’s clinical benefit. The required study is designed to assess whether Exondys 51 improves motor function of DMD patients with a confirmed mutation of the dystrophin gene amenable to exon 51 skipping. If the trial fails to verify clinical benefit, the FDA may initiate proceedings to withdraw approval of the drug.

      Whether this means FDA will actually withdraw approval of either eteplirsen or golodirsen remains to be seen. So FDA decided to require another study of both drugs while approving them.

      If a larger study’s still a must-have and FDA says they want to see proof of efficacy in that study or they’ll withdraw approval, perhaps this is to get the insurance companies to pay for treatment while efficacy is still being assessed. It’ll be interesting to see if the insurance companies actually do pay for either drug while they’re in a post-marketing study status to determine efficacy.

  4. Anon says:

    @ An old chemist : As someone who worked in the small molecule drugs for 20+ years, I fully agree with your views. From the litigation point of view I wonder how many lawsuits are out there for “biologic” based medications? I am not talking about companies “duking” out each others for IP violations etc. In my living memory the small molecules invited several law suits by the ambulance chasers (Vioox, Prozac etc.). Much impetus was provided as science advanced, but working on biologic based remedial measures will also put out ambulance chasers out of business. Meaning less liabilities. I could be wrong!

  5. Hap says:

    The Texas City ammonium nitrate explosion (for How Not To Do It)?

    I don’t think biologics will make drug liabilities go away – the drug companies have the public standing of tobacco companies and so will be targets for litigation no matter what happens. I assumed, though, that biologics are harder to make generics of and so effectively have longer periods of exclusivity than small molecule drugs, allowing companies to make more money from successful biologics.

    1. Lambchops says:

      Some comment on the contrast in uptake of biosimilars in the US and other markets such as Europe may be interesting. There’s a stark contrast there and how much of this is due to potentially confusing terminology from the FDA (‘interchangeable’ vs ‘similar’ and so on), the US legal system (which seems to essentially lead to out of court settlements which delay the launch of biosimilars), and deals struck by the pharmacy benefit manager middlemen would be quite interesting.

  6. Badgerchemist says:

    Not a comment related to blog posts specifically, but given the incredible breadth of experience amongst the readers of this blog, a running post to consult for experience/opinions regarding certain reactions and reagents would be a wonderful source for practicing chemists.

    1. Nameless says:

      A good place to plug this knowledge base “Not Voodoo”. It includes nice little tricks like how to work up LAH reductions without getting a unfilterable mess (“Pfizer workup”) and other tios for daily life in the lab.
      Link in handle

      1. anon the II says:

        I’m getting to be an older gentleman, so I’ve been around for a few years. I had never heard of the “Pfizer workup” before. So I looked it up. Well gee whiz, it’s the workup from Fieser & Fieser volume 1 under LAH. I’ve been using it for 40 years. Is it really the Pfizer workup? I sent my copy of Fieser & Fieser, volume 1- 17 or so off to a guy at Cubist pharm before they got bought. So I can’t look it up.

        By the way, I’ve got a few other antiques sitting around the house if anyone is interested.

        1. Nameless says:

          No, I misspelled it. Problem with mostly hearing about it and not reading it.

        2. Anonymous says:

          I also noted the similarity F&F Vol 1. I am guessing that Nameless HEARD someone mention the name of the workup and confused “Pfizer” with “Feiser”. But then that depends on how you learned to pronounce Louis’s and Mary’s name: FIE-zer or FEE-zer. I play it safe and refer to their works as “fee-zer and fie-zer.”

          1. Rhodium says:

            Mary pronounced it FEE-ser. By the time I met Louie he had a stroke and was not saying much.

        3. An Old Chemist says:

          I have heard this LAH reaction work up being called the ‘Fieser Work-Up.’ by eminent chemists at Harvard.

      2. Stanislav Rádl says:

        The first steps of the workup are identical with an old workup described by V. Michovich and M. Mihailovich in their book published in 1955 in Beograde. Its Russian translation from 1957 are well-known (Lithium Aluminum Hydride and Its Application to Organic Chemistry (Alyumogidrid litiya i ego primenenie v organicheskoi khimii) Moscow (1957).). The Fieser’s one ads stiring with magnesium sulfate.

  7. David Lilienfeld says:

    What’s become of gadolinium contrast agents? They remain on the market, and gadolinium–a fibrosing inducer–remains trapped in the CNS of more than 30 million Americans (never mind the ROW). What is it doing there?? Are there implications for getting drugs into the CNS? At least there would be some positives for NSF outbreak if that were the case.

    1. anon says:

      Dave, I can shed some light, as I am following on these issues as a scientific curiosity, but I am not an expert. That NSF outbreak in terms of Gadolinium toxicity in contrast agents (MRI scan) is too small over 25 y this has been tracked in comparison to the dose administered. It garnered lot of attention because actor Chuck Norris claimed that contrast agent used in his wife’s MRI poisoned her and made her sick. He and his wife, then sued the makers of the agent, seeking $10 million in damages. And then next thing we know is that this news was spreading like a wild fire. Further studies in the US and in Europe in this area has revealed that it is a question of preference for “Gd” and whether to go with open or closed ligands. The closed one like DOTA (macrocyclic) are pretty safe, less toxic and still in use. It’s the open (linear) one wherein “Gd” leaks and in few cases causes NSF and this is mostly seen with people who have severe CKD. Since 2009 no new cases of NSF has been reported and these contrast agents are to be avoided for the people with renal failures. Then there was another lawsuit of “Gd” deposit in the brain, but these do not cause AD and other Parkinson symptoms as was erroneously claimed. Bayer did extensive work in this area. But further debate on these issues are warranted.

    2. David says:

      More on gadolinium: Splendiani et al Insights Imaging. 2019 v10: 82 demonstrate Gd accumulation in brain following multiple administrations of macrocyclic agents. Based on other reports, the level of Gd accumulation appears to be much lower for macrocyclic than for linear agents, and linear agents have been removed from the market in the EU (and in practice no longer used in US). There remains no clear link between deposition and clinical signs or symptoms. The most recent communication on the from FDA that I know is http://www.fda.gov/media/116492/download
      Disclosure: I’m a neurologist, but not specifically an expert in this area. No conflict of interest.

      1. old chemist says:

        As someone who worked on the process development of Gadoteridol back in 1987, the one thing that I would mention is that the compound was very difficult to assay for purity, the ligand in particular. It was too polar to use reverse phase because it didn’t stick even with 100% aqueous buffers. It was too polar for normal phase because it would never come off the column and I wound up using a polymeric column at the time to get it to stick to something but we didn’t have the fancy detectors that are available now. Just UV at 220 nM. It also didn’t have any chromophore whatsoever so you just got end absorption. That means that all these agents were developed and approved by the FDA with, by today’s standards, poor analytical assays. So even if the free Gadolinium in the API is low because it is all chelated to something doesn’t mean that an impurity won’t chelate to a different metal in the body when administered thus delivering free Gadolinium which is very nephrotoxic. For instance, some of the impurities bound calcium better than gadolinium. I do wonder whether any of these toxic events were ever tracked to certain batches of the API or if it was just random. (This is the first I am hearing about this NSF outbreak.)

    3. Lambchops says:

      Non-neurologist here but done some work related to this. From a European perspective my understanding is that the agents specifically linked to safety concerns are no longer on the market and that in theory clinicians are happy to use Gd. However, there are residual safety concerns among clinicians which can mean they are hesitant to use Gd contrast agents unless absolutely necessary and as a result of this Gd-enhanced MRI scans aren’t always available across all hospitals. Has some implications in areas like multiple sclerosis where Gd is an option to to diagnose certain stages or sub-categories of the disease.

  8. C says:

    Would love to hear your thoughts about the DIY clinical trials of CBD that are sweeping across the US!

  9. Barry says:

    Therapeutic ‘phage needs more discussion.It’s not clear how to patent/own/monetize/regulate a therapy that keeps mutating. But as the great age of antibiotics fades in the rear-view mirror, we need to explore all avenues for infectious disease.

  10. Oligodendrocyte expert says:

    The authors of a recent SCIENCE paper elegantly demonstrate that human plasmanylethanolamine desaturase activity resides in the TMEM189 protein. This discovery solves a longstanding mystery surrounding the hallmark sn-1 vinyl ether bond found in plasmalogens, a subset of ether lipids. Plasmalogens are key players in the long-term stability of CNS myelinated axons. The integrity of myelinated axons—which, it should be emphasized, are present in both gray matter (GM) and white matter (WM)—is critical for cognitive function. A post on lipid biochemistry, particularly with respect to this interesting finding, would be GREAT.

    Happy Holidays Derek!

    https://science.sciencemag.org/content/366/6461/128

  11. loupgarous says:

    Not a pharm issue at all, but definitely chemistry-related (if inorganic):
    A team at Boston College has announced that they found the Weyl metal tantalum arsenide converts incident photons to light at ten times the efficiency previously achieved. The effect is seen in the mid-infrared range, which may point to applications in IR sensing or even PV generation of electricity in what we now consider “waste heat”.

    Interestingly, electron chirality is cited as central to the effect observed by the Boston College team. Usually, chirality refers in this blog to the direction in which polarized light is rotated in enantiomers of the same compound. Electron chirality is involved in liquid hydrogen (if I’m using the term correctly) – in his book Ignition, John Clark noted that reversal of electron spin accounted for LH2 self-heating after standing a while.

    1. eyesoars says:

      I think you’re referring to the spin isomers of hydrogen? Which refers to the nuclear spins (not electron spins) of the hydrogen atoms in a hydrogen molecule. The relevant bit to rocket fuel is that the states are metastable, but the ortho version contains enough energy to vaporize about 2/3 of a freshly-made batch of liquid hydrogen. Thus processing with ferric oxide or other catalysts to promote transition to the para isomer during processing.

      1. loupgarous says:

        Thanks for the correction. It’s of more than academic interest to me… not a twenty-minute drive from where I live, bulk liquid hydrogen is transported (I think by barge) from where it’s made in southeastern New Orleans to Stennis Space Center, where it’s used as fuel for large rocket engines being tested prior to use in boosters to orbit payloads. Thankfully, the nuclear spin issue with LH2 had a fix it seems to be working.

        When I hear one of the really large engines which runs on LH2 and LOX (or other fuel combinations used, say, by parts of SpaceX’s Raptor or Blue Origin’s BE-3) rumbling loudly from 20 miles away, I keep thinking of what would happen if a first or second stage detonated instead of firing as designed. Nothing like that’s happened since 1966, when a hydrogen tank on a Saturn V second stage S-II-T ruptured during pressure tests – an enviable safety record, better than that of the petrochemical industry surrounding Stennis.

        1. loupgarous says:

          Last sentence should have read: “…I keep thinking of what would happen if a first or second stage detonated on the test stand instead of firing as designed. Nothing like that’s happened since 1966, when a hydrogen tank on a Saturn V second stage S-II-T ruptured during pressure tests…”

  12. Anon says:

    What’s the latest news on delivering proteins into cells? Any breakthroughs in that area?

    1. Barry says:

      The phospholipid bilayer was invented a few billion years ago to compartmentalize things like proteins. If it weren’t very good at it, life would be impossible.

      1. CNS guy says:

        I guess a few billion years ago the scientists weren’t around….
        Luckily, they are now.

        Receptor-mediated transcytosis at the blood-brain barrier is a CNS drug delivery strategy
        https://www.ncbi.nlm.nih.gov/pubmed/24411731/
        https://www.ncbi.nlm.nih.gov/pubmed/24411725/

  13. angrygecko says:

    How about “TIWWW the Movie”? OK, I’ll settle for the book version.

    1. Stuntman says:

      He might have difficulty making that movie if its all about him not working on the essential bits.

      1. loupgarous says:

        PBS is full of documentaries by scientists not actually doing anything they became famous for while on camera.

        The producers of “TIWWW: The Movie” would just need to let Derek (or a professional voice-over guy) read TIWWW columns aloud as the soundtrack for footage of horrible, horrible things like that production run of pure liquid hydrogen cyanide he once described, then cutting to footage of what cyanide does to, say, coyotes.

        Family television, folks.

      2. loupgarous says:

        I’m also thinking that some of Derek’s more vivid similes/metaphors for Things He Won’t Work With, such as

        “Synthesizing polynitro compounds is no chocolate fondue party, either: if you picture a bunch of guys wheeling around drums of fuming nitric acid while singing the Anvil Chorus from Il Trovatore” pr
        “cocaine-soaked cobras”

        require a movie or television documentary to do them justice.

        As much as I’d love to write that screenplay, WGBH at Boston does that sort of thing already – it’s called “NOVA“, and they’re really good at it. I hate the idea of condensing TIWWW into one or two hours, but it would make a killer NOVA episode.

  14. Grad Student says:

    Didn’t want to bother you again about it, but holidays might be a good time for shared musings from you & the readership on a question you were kind enough to weigh in on by email a few weeks back:
    “What is starting one’s career in Boston/SF these days “worth” in terms of the network one can build and the proximity to other companies, institutions, etc.?”

  15. Joy says:

    I’ll second the request for insight into the latest industrial accident or three, and also request another look into global supply chains/NDMA/quality control assays: what progress? what should be done to prevent similar occurrences?

  16. Andreas says:

    More Things I Won’t Work With would be great. They are hilarious and have taught a non-chemist like loads of valuable things, such as:
    – Nitro groups is bad news
    – Fluorine is evil

    1. teflon says:

      fluorine is evil?

      1. BernYeeFluorines says:

        Yes Fluorine is evil. Some Fluorine based drugs don’t degrade and cycle in the environment.

        So Derek, how about a post on how organic persisters are changing the endocrine systems of flora and fauna worldwide- as compounds like Prozac cycle in and out of organisms-

        It may be good for patents and drug activity, but they sure aren’t good for the environment.

        Qw, My Endocrine System!

      2. PFOS PFOA et al says:

        @Teflon: Fluorine and interhalogen fluorinating agents such as chlorine trifluoride, chlorine pentafluoride and bromine pentafluoride will suffice for evil until Pure, Inchoate Evil comes around.

        Derek’s shared with us how fluorine and fluorinating agents are both horribly corrosive to the skin and lethal metabolic poisons (due to their affinity for the body’s stores of calcium, which is vital to function of nerves and muscles – including the heart).

        Per-and-polyfluoroalkyls such as PFOA and PFOS, once ubiquitous as components of Scotchgard® and Teflon® among other consumer and industrial products, are being withdrawn from production and use. This was after chemical and epidemiological studies in and around the plants where 3M and Dupont made them revealed they’re as nonbiodegradable as compounds can be and insidious toxins and carcinogens at low levels of intake.

        Derek’s also discussed the toxicity of the fluoroquinolone antibiotics here

        So, yeah, fluorine’s made its bones as an evil chemical. It has its uses, including being a component of a lot of important drugs and other chemicals. But it ought to be handled with respect, suspicion and wariness.

        1. Teflon says:

          Do you guys brush your teeth?

          1. loupgarous says:

            Odd you mention that. When I was on a trial of everolimus for neuroendocrine cancer, one of the things that I had to do was go over to a toothpaste with NO sodium fluoride in it, because everolimus’s adverse effects include problems with the lining of the mouth, and NaF apparently drives that right along.

            Notice you’re told on the label not to swallow fluoridated toothpaste or mouthwash. That’s because, while in small amounts, and confined to the vicinity of your teeth NaF makes your tooth enamel more durable by forming a thin layer of CaF, ingesting NaF does you no good, and might do you harm done often enough.

          2. Teflon says:

            Loupgarus,
            That’s exactly the point I was hoping to make.
            Yes, chemicals are toxic at some level. There is always a trade off between the desired and undesired effects. The key is to find ways to mitigate possible risks.

            If we learn new information, that balance may shift in either direction. And we can then decide what to do. History has plenty of examples of that.

            As a chemist with decades of bench work experience, and in a blog where I would expect a majority of chemists, I thought it was interesting to have an element broadly considered as “evil”.

          3. S says:

            Now there is even Stannous fluoride…

          4. loupgarous says:

            @Teflon: Andreas may have been thinking of Derek’s August 15th blog “Thanks, But No Thanks, which shows less than total affection with the idea of working with fluorine cells – “making it up fresh”, as it were:

            “Given a choice between making my own fluorine and trying to crystallize tellurium compounds, I think I’d choose. . .well, hold on a minute. . .truck driving school? Cleaning out grease traps? As a character in the old Pogo strip put it once, “No! I can always rob graves!”. If there were truly no other choice, I suppose I’d take my chances with the tellurium, which might well poison me a bit or make me a social pariah, but would not be actively coming to kill me every second I was in the lab (like the fluorine would be)…”

          5. Teflon says:

            For 2019, the US FDA approved 11 new small-molecule medical entities (NMEs) containing fluorine – that’s roughly half of all new small molecules.
            Of these 11, several contain many fluorine atoms in their structure. One has six fluorine atoms.
            Makes me wonder:
            1. Is fluorine really necessary to take every one of these compounds through the finish line?
            Or are medicinal chemists just including them fo fun?

            2. Are fluorine’s environmental effects so bad that they outweigh the therapeutic benefit on patients?

            3. What about the environmental effects of drugs containing other halogens, or no halogens at all, which may also be potentially bad for the environment? (not every compound lacking fluorine is degraded to CO2 and water)

            4. How do the amounts of these drugs reaching the environment compare with the tons of other chemicals produced across industries using corrosive or environmentally persistent substances, aren’t there higher priorities to take on? For example, how much TFA is produced annually?

            Also, a brand new JMC article on “A Systematic Investigation of Lipophilicity Modulation by Aliphatic Fluorination Motifs” at https://pubs.acs.org/doi/10.1021/acs.jmedchem.9b01172

            I guess pharma labs are filled with devils…

      3. sgcox says:

        I am pretty sure Andreas refers to this particular form of Fluorine:
        https://blogs.sciencemag.org/pipeline/archives/2008/02/26/sand_wont_save_you_this_time

        1. BernYeeFluorines says:

          Lets not confuse inorganic F with the organofluorines that are so in vogue in drugs these days. Prozac, 4F-fentanyl- and others are organic persisters that end up in the water supply.

          Its the strategic placement of a F or other fluorine group that needs watched and closely. They should break down in the environment and the FDA doesn’t look at this.

          1. Teflon says:

            BernYeeFluorines,

            Nobody is confused; inorganic fluorine can be toxic as well…

            I do not disagree about the fact that fluorinated drugs are reaching the waste stream.
            I just think this is a manageable risk, and yes, we should do something about it. I just do not see this risk as comparable to other environmental hazards.
            Besides, I bet you are probably more concerned about global warming than prozac in tap water. I am.

          2. BernYeeFluorines says:

            NoTeflon- I don’t believe in Global Warming. The atmosphere is the best its ever been.

            4 billion years ago if you went outside your lungs would sear shut from gaseous ammonia.

            Plus if humans disappeared from the planet Mother Nature would rejoice. Its the other organisms that deserve a break, and hitting them with endocrine changing doses of Prozac isn’t fair- since its a drug that may or may not even work-

          3. loupgarous says:

            @BernYeeFlourines – Precisely the issue with PFOA, PFOC and other polyfluoroalkyl compounds. They out-gas from Teflon® (especially in cooking pans and utensils), ScotchGard® and other consumer and industrial goods (like flame retardant foam at airstrips) and are very durable in the environment – not biodegradable, but among those potent endocrine disruptors and carcinogens you spoke of earlier.

            Likewise, fluoroquinolone antibiotics cause fragility of collagen-containing structures to various degrees depending on the specific compound and how susceptible the patient is receiving it (my wife had a bad tendon tear not long after getting Levaquin). People over 60 tend to be more susceptible and have more catastrophic damage, including aortic dissection.

            So your remarks are spot-on – it’s probably time for a comprehensive post-marketing review of reported adverse events after administration of fluorine-containing pharmaceuticals (someone else pointed out here that a French review of the literature in the 1990s drew early attention to the issue, but only after the Toronto and Taiwan studies did FDA start requiring black-box warnings on the fluoroquinolones most commonly associated with severe AEs).

  17. Nick K says:

    I would love to see more “How Not To Do It” posts. They light up my day and help ease the distress I feel when I remember my own blunders and embarrassments.

    TIWWW posts are also pure gold.

    1. sgcox says:

      Went to some old ““How Not To Do It” posts in nostalgia and noticed that Acetylene Explosion has no working link. But it is still on youtube:
      https://www.youtube.com/watch?v=RoatgaQrK28

  18. Hungry_Chemist says:

    As it’s the holiday season and the best time of year for sharing, I would love to have more scientific cooking recipe posts.

    Another vote for TIWWW as well. We already have a movie and book request here, but when is the Netflix serialization happening?

    1. loupgarous says:

      If NetFlix or Amazon won’t bite, I’m thinking a TIWWW miniseries might be crowdfunded – chemists are a niche market, but there are many fans of TIWWW who never got past college inorganic lab who might chip in. A miniseries format would be just the thing – half-hour to an hour episode per column.

      1. Chris says:

        I’m just a simple country pharmacist, but I love TIWWW. I’d love to see a book version most of all.

  19. Any insights into this one(?): A report on endpts.com today mentions a new company called Epirium is being started by some former Genentech and BMS people to commercialize “a new human hormone” that supposedly slows mitochondrial loss in muscle tissue. The article mentions a previous company called Cardero that was somehow involved with the same IP. ClinicalTrials.gov lists 4 completed trails run by Cardero on epicatechin for Duchenne MD, Becker MD and Friedreich’s ataxia. The new outfit (Epirium) apparently just closed an $85M series A round of funding. Real science, or another Sirtris?

  20. Franck says:

    It would be great to know Derek’s take on academic drug discovery. The NIH roadmap is almost 20 years old. A lot was invested in infrastructure and people. Has it delivered bang for the buck?

  21. What do you think of IRIS – infra-red ion spectroscopy – as a way of getting structural info about molecules (link to a review in handle)? Seems a fiddle at the moment, and requires a Free Electron Laser, but has the potential to give the information content of IR with the sensitivity of detection of MS.

  22. Med chemist says:

    What about a post on the use of CRO’s for drug discovery research? How it’s evolved and experiences that have been had?

  23. An Old Chemist says:

    How about discussing whether Derek Lowe should be awarded a Pulitzer Prize for being a pioneer science blogger about the pharmaceutical industry (its all aspects). If the Nobel Prize committee can make an exception and give the literature prize to a song writer (Bob Dylan) and a to a short-story writer (Munroe), then Pulitzer prize committee can also give it to Derek for a new kind of literary stuff. Siddharth Mukherji got his Pulitzer for his book ‘Biography of Cancer: the king of all the melodies” which was a well narrated overview of cancer over the centuries.

    1. loupgarous says:

      Much of this blog covers new developments in medicinal and other chemistry in their historical context… wonder if the Pulitzer Prize people would be open to rewarding Derek’s encyclopedic knowledge of those fields in the same way they awarded Richard Rhodes a well-deserved Pulitzer in history for his book The Making of the Atomic Bomb. Eventually, journalism, of all fields, should reward excellence in blogging. After all, important news breaks in blogs and social media more and more often.

    2. loupgarous says:

      Much of this blog covers new developments in medicinal and other chemistry in their historical context… wonder if the Pulitzer Prize people would be open to rewarding Derek’s encyclopedic knowledge of those fields in the same way they awarded Richard Rhodes a well-deserved Pulitzer in history for his book The Making of the Atomic Bomb. Eventually, journalism, of all fields, should reward excellence in blogging. After all, important news breaks in blogs and social media more and more often.

  24. Dan says:

    Is it still possible to get per-category RSS feeds?

    The Things I Won’t Work With feed I had subscribed to in the past has stopped working and I can only find the master feed with all of Derek’s articles and per article comment feeds now.

  25. JG4 says:

    BTW, Happy New Year. I offer two terms of art to enrich the discussion. Appreciate very much the discussion and the skepticism. I heartily endorse this blog in general and TIWWW in particular.

    “Perfluordisaster” unleashed by our chemist friends with some help from DoD. We’re going to need some new life forms that sequester these and many other toxic compounds from soil, our guts, and our food for “easy” recycling.

    Speaking of DoD, “angel carts” are used for transporting liquids exhibiting catastrophic runaway from the slightest cavitation. They have soft rubber/pneumatic tyres and roll on wooden ramps that can be replaced quickly when they are reduced to splinters. Much less dangerous than the steel that otherwise would be thrown around.

    “Distilled essence of hell” would fit neatly into TIWWW.

    It would be a nice touch if the RECENT COMMENTS text were itself a hotlink to a separate page showing the first n lines of the recent comments, in order of time.

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