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A Word on Blog Topics

I’ve had some queries that make me think that a brief meta-blog entry might be in order. I’m still fielding a lot of coronavirus queries, not all of which by any means make it up here to the blog. And at the same time, I’m also getting a lot of suggestions that are more in the classic mode: interesting science and drug-discovery stuff that has nothing to do with the pandemic.

Readers have probably already noticed that there have been more of the latter recently. That’s going to continue. I am still going to write about big coronavirus issues, but in the end, this is not a Covid-19 site, and thank God. No doubt I’ll shed some of the readers that I’ve picked up over the last year or so, people who are looking for more pandemic-focused material. That’s fine. Such posts are still going to show up here, but you may or may not want to go through multiple posts on organic chemistry, chemical biology, drug discovery and development issues in general, and so on before another comes back around.

On the other hand, you might find some of those interesting – who knows? I’ve picked up a lot of regular and semi-regular readers over the years who started out reading the blog for other reasons than the ones that have kept them around. And that’s fine, too, more than fine when you get right down to it. Over the years, I’ve tried to vary the topics that come up so that if someone finds themselves uninterested in a given post, that they can be pretty sure that the next one won’t cover the same area and will be worth checking out. That rotation got thrown out the window over the last few months, of course, but at the same time there was certainly a lot of interest in All Things Coronavirus, so I didn’t let that bother me.

But at this point, the way out of the pandemic seems clear. The vaccines work. We have to produce and distribute huge amounts of them around the world. If and when we are able to do that, I really believe that the pandemic has excellent chances of being over. Really over. There are a number of things that can go wrong with that, of course, and one of the big ones would be the emergence of a variant that truly evades the immune response brought on by the current vaccines. I am very hopeful that this will not happen, but neither am I willing to bet the future of the world on that hope, either. We need to get the population of the world vaccinated, to knock things down and lower the chances that such a variant can come up.

The corollary to all that is that yes, I believe that the vaccines both work and are safe enough to roll out into billions of people. It has not escaped my notice that there are people who disagree with that statement. With both parts of it, and especially the second. But at this point I would like to quote a long reply I gave deep in the comments section of this post, which I suspect few people saw (and I don’t blame them!)

. . .I’m getting so many questions from people who are nervous and skeptical about taking the vaccines, and these seem to be coming from several different sorts of people. Some of them are looking for ways to feel better about making the decision to get vaccinated, while others are looking for reasons *not* to take it. And addressing all these objections as a series is not necessarily doing much good.

I’m fond of saying that you can’t use reason to argue someone out of a position that they did not arrive at by reason. And some of the objections I’m getting are coming more from the emotions, and can’t really be dealt with by a step-by-step quoting of medical rationales with recourse to literature references. It’s the wrong tool for the job.

If you’re looking for complete assurance that nothing bad will happen, I can’t give it to you. But that goes for any medical intervention at all. Take antibiotics: if you have never taken a beta-lactam, I cannot assure you that you will not be one of the rare people who will have a strong (possibly fatal) anaphylactic reaction to them. If you take a fluoroquinolone instead, I cannot promise you that you will not be one of the people who have a bad reaction in the joints and tendons. If you opt for clindamycin instead, I cannot promise you that you will not then get a strong (perhaps deadly) C. difficile infection in your gut – that happens, too, on rare occasions. The same goes for any other therapy, for any other disease.

But the paper you cite isn’t talking so much about rare idiosyncratic side effects, as much as something that should affect (unless I mistake their language) a large number of people taking any of the Spike-protein-producing vaccines. But the real-world data aren’t showing it. Now, one response to that it “Well, you haven’t waiting long enough”. But from what we know about the pharmacokinetics of the vaccines, the people who were vaccinated earlier this year should be *long past* producing Spike protein by now. And we’re seeing no such effects in them. The authors say “long term” effects need to be watched for, but “long term” is in the eye of the beholder. Coronavirus infection itself can bring on lung trouble far more quickly – shouldn’t we have seen something by now? I find it very difficult to believe that a one-time pulse of Spike protein alone sets people on an irreversible course towards pulmonary hypertension, etc.

So I think that the hypothesis advanced in the paper has not panned out. Most medical hypotheses don’t, even ones that are backed up by far more reasoning and far more data than this one. It’s not a crazy paper, but it’s not irrefutable either, not by a long shot. Over the last 30 years, I have learned that even my best ideas get brushed aside by real-world data, and I don’t take it personally. But this argument will not be persuasive to someone who is worried about the idea of getting a coronavirus vaccination in general. They either will not accept this response, or will wave it aside and move on to the next objection: “Well, what about this? Can we be sure that this other thing won’t happen?” It never stops.

If we continue to see no signs of lung damage for another month, will that put you more at ease? Three months? Six? A couple of years? You will need to pick the point at which you will feel convinced. For some people there isn’t one. For my part, I found the clear and present danger of the coronavirus outweighed any objections to the vaccines that I could come up with.

That was in response to a question about a particular paper, but the general points apply. I am deliberately not turning this site into a Whack-a-Mole exercise dealing with a series of objections to some of the coronavirus vaccines, or all of the coronavirus vaccines, or all vaccines for anything ever, or germ theory in general, or ontology and the knowability of any facts whatsoever. If you believe that the coronavirus vaccines are going to start scything down the human population Any Day Now, there’s not much I can do for you. Build that bunker, stock up on potable water, dried beans, and potatoes.  Meanwhile, I very strongly believe that the rest of the world will be working its way out of this horrible pandemic.

I’ll still be writing on major issues relating to the coronavirus and the therapies and vaccines against it. But any attempt at blow-by-blow coverage is over here, and has been over for weeks. Please feel free to hang around and pick up some weird knowledge about science and drug research; some neat stuff comes up every once in a while. At the other end of the scale, though, all I can say is enjoy the spuds.

112 comments on “A Word on Blog Topics”

  1. Michael Mandy says:

    Can we get more of “Things that I won’t work with”? They are always light posts and fun to read!

    1. Not a Doctor says:

      This was how I found the blog, via XKCD’s citations when discussing FOOF.

      1. Lamont says:

        I’m just here for more of Satan’s Kimchi

      2. Tom Maneiro says:

        Bring back the nitros!

        Came for the nitros, stayed for the (corona)facts, but I really need more Things That Blow Up and less zinc/HCQ/Russian trolls/whatever is the last social network-induced fad. Life needs joy, after all. But more importantly, more nitros!

        1. Ken says:

          As a compromise, how about a crossover topic? For example, what happens if you mix powdered zinc with FOOF?

    2. Al says:

      I second that, excellent and funny pieces! They remind me of my PhD student year when I discovered this blog through those (and then attending a Klapotke lecture and trying not to smile too much when seeing the now-familiar structures), and are a great way to get some of my colleagues interested in lab safety, curious chemistries outside of our niche overspecilaized field, andgenerally lighten the mood at the coffee corner!

    3. I’m torn. I loved those posts, but at the same time “Do that same thing I like that you’ve done dozens of time before!” isn’t exactly a good way to learn new things. And we all need to learn new things.

      (And, “Freebird!”)

    4. Tom A says:

      Yes Michael. I was going to make the same point. Also a related topic about improbably crazy health and safety risks one took because of ignorance at the time. I myself feel lucky I’m still alive at 70, but with kidneys and liver compromised, after working with formaldehyde, pentachlorophenol and many other chemicals.

      1. dearieme says:

        My first PhD supervisor told me, after he’d taken an extravagant risk, “I think I’ve become immune to such things”.

        OK, matey, you’re immune to it. What about the rest of us? A lab tech ended up in hospital.

        There’s no vaccine for extreme selfishness, bundled up with stupidity and (presumably) a touch of insanity.

    5. FoodScientist says:

      Do a post on Covid/infectious disease Gain Of Function Studies!!! (A lot of people probably wouldn’t work with it)

      It seems a little too risky pre-pandemic, but we really should be doing these kind of studies now. I don’t think Covid will be eradicated from every population/location in the world any time soon. It will probably become endemic.

      Gain of function studies seem like the only way to win. This way we could make a vaccine/booster that covers mutations known 8 months ago when development began; but also mutations likely to occur in the year after development started.

    6. Paul says:

      Ha, when I finished reading this blog post, I wanted to comment for the first time to request another “things that I won’t work with” entry to cheer all the readers up, now that we are moving into a new era of pandemic coverage on this blog.
      Then I scrolled down to the comment section… 🙂

    7. Silverlake Bodhisattva says:

      Another vote for TIWWW

  2. David Young says:

    How about a blog on the new LAG-3 inhibitors for cancer. Looks like Bristol-Myers and Merck are on a race to get their’s approved.

    1. Josh says:

      Seconded!

  3. MoMo says:

    I think I speak for the Pharma crowd that we want to get back to the good ole days of ITP, discussing new therapies, how drugs really work, complaining about academia and industry and the basics of medicinal chemistry. I’d even relish an argument or two over AI, combichem or other science fads at this point. Good job on the Covid details too- you must be exhausted by it and wake up screaming about it scaring your household- But we all hope to get back to normal whatever that is at this point in medical history.

  4. sgcox says:

    I suspect there will be a lot of traffic here soon about Alzheimer.
    Almost to the level of Covid.
    Whether aducanumab approved or not..

  5. David says:

    I came just out of high school for Things I Won’t Work With/Touch, stayed for everything else!

  6. In Vivo Veritas says:

    I’d love a post on NASH, as how many failed Ph2/3 trials it’s left in it’s wake. Regulatory issue? Basic disease misunderstanding? Crappy animal models? FDA wants the wrong endpoints? I think NASH is becoming the new AD. 🙂

    1. Derek Lowe says:

      Definitely worth a look – that one has left a substantial pile of wreckage, joining Alzheimer’s (the king), CETP, sepsis, stroke, non-opioid analgesics, MMPs, and a number of other tar pits full of bones.

      1. metaphysician says:

        That sounds like a potential topic itself: lesser known hard targets in medical research, and what makes them hard.

  7. Humble Scrivener says:

    More olfactory and essential oil chemistry and Things I Won’t Work With, please.

  8. Brian says:

    For whatever it’s worth, you’ve done a wonderful job on the COVID stuff. It has left me a LOT better informed about the pandemic than I would have been otherwise. THANKS.

    1. Mike M says:

      I second this statement

    2. Roland says:

      This. Thank you so much Derek! I came for the Covid/vaccine info but will be staying for the other content since it hits a rare combination of readable, informative and grounded, and always on interesting subjects.

  9. tt says:

    Really well put post about the vaccine doubters. Every time I am about to engage, I come to much of the same conclusion that your articulated above. It’s a fool’s mission to appeal with data and logic to those who have already reached a conclusion and are only seeking out evidence to confirm it, no matter how thin (similar to the whole HCQ truthers). In the meantime, I will just rejoice in the amazing science and superhuman effort it took to get this vaccine into my arm in about a year’s time. I truly believe it is one of the greatest scientific and technical achievements in history for our industry. We should all take a moment just to reflect on that, as I think the written history of this period will.

  10. JasonP says:

    eh, hate to be “that guy” especially when the pivot to all Covid-19 all of the time was most useful and helpful and much appreciated by this chair….That came at a time when we all needed good information, and education and some calm insight into the topic.

    But it sure rubs me the wrong way to see smart people give up and quit with “you can’t use reason to argue someone out of a position that they did not arrive at by reason” kind of stuff.

    Is that the only tool in scientists intellectual tool box? I mean if the smart people can’t figure out a way to “educate,” help along, bring the light to or something else then who is going to do it? The “dumb” people? There has to be an approach that works or can work better. Isn’t that what scientist do, if one thing fails, try something else?

    Y’all have the training, experience and knowledge to know what could happen if this vaccination campaign fails. Why not shift some focus to find the message that resonates? I think we all have an obligation to do more than just get own own shots. Use the acumen you were gifted with to solve this “final problem” of the pandemic.

    ~Stepping down off soapbox~

    1. tt says:

      yea…I had much the same thought initially, but I also am a bit self-aware that I personally stink at dealing with irrational arguments. It’s just a skill I’ve never quite honed as I tend towards sarcasms and impatience when dealing with them. I do wish we had more public advocates of science that people actually trust and listen to, but the politicization of this has made it very difficult to find advocates with broad appeal. The best I can do is convince people close to me and my extended family, but beyond them, I would likely do more harm than good for the cause.

    2. Eugene says:

      So often I have found that people with higher education in specialized fields communicate in a manner that excludes people not in their specialty. So often to untrained people it sounds condescending and frankly insulting. Telling people that they have informed consent and they have the right to make their own decision without the information they need to make those decisions makes the condescension all the more infuriating. I have had numerous conversations with people that don’t have a background in Science and have come to understand that much of the Science communication is either simplified to the point of being useless to untrained public or way over there head just from the questions I get.

    3. Mammalian scale-up person says:

      I suspect the answer to this is, you can’t be an expert in everything and it is a rare person indeed who has mastered both the science of pharmacology and in this case immunology and epidemiology AND group psychology / sociology. Getting communications out clearly to a populace with a wide range of education and backgrounds is not trivial and is a whole field of expertise all by itself, and we all only have so much time on earth to spend on any given thing – it’s asking a lot that we cure or prevent horrible diseases AND take on the role of Chief Communications Officer. That’s more than two full time jobs there, and humans have to sleep and eat sometimes.

      Sort of like we also are tasked with being Diversity Committee Experts if we’re not white or male or straight, and Impromptu IT Support for the spreadsheet-impaired, and if we get declared supervisors we now also have to become instant budgeting and capex managers overnight: these are actual job skills that normally you’d have to pay someone a large pile of money to take on, not really volunteer positions. Just like you wouldn’t want your car designed by someone who merely tinkers with a 3D printer as a hobby, or your complicated tax return done by your beer buddy opposed to a CPA, you probably want a real professional communications person to craft messages to reach a hugely diverse audience. And that communications person is going to charge big bucks for their services, as they should if they are good at what they do.

      I mean, the short answer is basically yes, scientists are NOT taught pedagogy in school. We are taught about evolution, chemical reactions, energy balances and thermodynamics, a great big pile of math, physics, taxonomy and how to use various instruments and techniques to find things out about the world, plus various internships and research. There’s not a ton of spare time to squeeze a few semesters of pedagogy and communications in there. Already biomedical PhDs in the US run to 7 years of more than full time work, on top of the 4-5 years of undergrad / 5th year MS we typically do. Telling someone they need to make that 7 years into 9 for the benefit of being able to clearly tell Joe Shmo that he needs to get a shot in the unlikely event of a once-a-century pandemic, when Joe Shmo’s primary care physician and public health authorities have already been explicitly given that responsibility, is not going to go over very well I think.

    4. theasdgamer says:

      You might have a look in the mirror sometime.

      Anyone who believes that late treatment with an antiviral was ever going to work would also believe in the Tooth Fairy.

      Scientists are often at odds over theories.

    5. SR says:

      Isn’t that what all those people over in sales and marketing are for? Maybe the pharma companies should be sending out cute reps to take anti-vaxxers out to lunch?

    6. Jim Van Zandt says:

      Rather than playing whack-a-mole with objections, I suggest asking something like “who do you respect?” Then see how many of those people have gotten vaccinated. For example, Donald Trump got vaccinated in January. Personally, I don’t respect him, so his choice didn’t influence mine. But if the doubter you’re talking to respects Trump, or Joe Biden, or Barack Obama, or Mitch McConnell, or Willie Nelson, or Arnold Schwarzenegger, or The Dalai Lama, or Pope Francis, or Hank Aaron – all of whom have been vaccinated — then maybe following their examples will start sounding better.

  11. steve says:

    I’d like a column on the science of homeopathy and its synergy with Reiki energy manipulation and polarity therapy. For some reason I’ve never seen you dwell on that topic in depth. There is obviously something happening there on the quantum level that allows for harmony with the universe. I would think a medicinal chemist like yourself would be all over that. Must have something to do with pi vs sigma bonds…..

    1. Amedeo Vetere says:

      Great example of sarcasm😂😂!!!

      1. theasdgamer says:

        Actually, since vaccines are based on homeopathic principles, it’s hilariously ironic.

        For those who don’t know homeopathic principles:

        1. Like heals like.

        2. Weaken the pathological principle (often by dilution)

        Attenuated (weakened) viruses are used to develop immunity.

        1. steve says:

          Oy. Please stop displacing your abysmal ignorance. Vaccines and homeopathy have absolutely nothing in common. Please take your meds, have the nice nurse tuck you in and stay off line. Thanks.

        2. M says:

          I’ve found it! The worst thing on the internet!

    2. eub says:

      Hey, we could have a clinical trial update on Nativis and their photon-field activation of water to have pharmaceutical effects!

      https://blogs.sciencemag.org/pipeline/archives/2010/06/02/the_power_of_photons_you_say

  12. Smokerr says:

    Great site, not my area other than Vaccines in general and I got directed here due to Covd.

    I will check in, mostly for updates on what the findings are and the break down for an informed reader but not remotely an expert as you put it in terms that are easy to understand. Call it a trusted source.

    As for risk, I alwyas laugh when the focus goes to a tiny risk and just being alive (or trying to stay that way) with ALL the things try9ing to do you in, is a huge one.

  13. John M says:

    I’ve been here for 12 years or so. I love the regular content and welcome its return. But I want to acknowledge what a huge public service you have delivered during the pandemic, with reasoned and (mostly) dispassionate presentation of very complex topics and (mostly) calm response to the innumerable crazies who showed up. I also think the few exceptions to “mostly” were warranted.

    I really think your body of posts on COVID-19 represent a significant contribution to public science education. Personally I’m very grateful for it. Thank you!

  14. anon says:

    I just come here for the recipes!

    1. Derek Lowe says:

      Now you’re talking. . .

  15. J Curwen says:

    I think Dr. Lowe is a real genius, and this blog is priceless.
    However, what I am missing in the covid arena, is an answer to possible worst case scenarios, something every risk manager does on an everyday basis.
    For example, we saw Dr. Jaenisch ambivalent behaviour concerning the integration of vaccine mRNA, first a feature now an impossible thing:
    https://www.medicaldaily.com/can-mra-vaccine-change-dna-459011
    Also the residual DNA: its linearized, not in plasmid form, its probably part of the LNPs (due to its charge). Vaccine Plasmid DNA has been found in gonads after intramuscular injection:
    https://pubmed.ncbi.nlm.nih.gov/16125283/
    Linearized DNA has much higher integration potential.
    I know that the risk for integration might be infinitesimal.
    But I really miss some guy with expertise or mathematical brain power who would explain to me why its surely no problem to vaccinate the whole young generation.

  16. Mostly harmless says:

    I would love to read a qualified opinion on the therapeutic potential of currently scheduled drugs (LSD, Ketamine, ..). There are any number of articles that claim they are the silver bullet for several illnesses(e.g. depression, anxiety attacks). And of course on the other hand there are any number of articles that dispute any positive effects beyond placebo effect. For a layman it’S hard to come to an educated opinion in these matters.

    1. Derek shared a paper on a post called FINALLY THE REAL MECHANISM SOR SSRIs. It was a brilliant paper that explained why ketamine and LSD work fast while SSRIs work slow. Finally a new target !

  17. tally ho says:

    Derek – thanks for all the Covid-19 related information over the past year-plus and counting! However, it will be good to have you back in the choppy water of medicinal chemistry and drug discovery. And hopefully this will translate to less time playing whack-a-mole reading through the bumper crop of trolls and aggressive contrail theorists that have appeared In the Pipeline in the course of 2020. Kahneman might say it’s a good time to dial down the noise.

    I second a blog on NASH – where has the pipeline been and where is it going.

    Also, it’s been a while since there was an installment about “Things that Smell” – can’t go wrong there. For example, what is the active ingredient in “fart spray”? Would butyric acid be a safer and more efficacious alternative? Would AI be able to distinguish?

  18. DRN says:

    Yeah, it would be a good idea to take it easy with the covid/vaccines… your blog is awesome on many levels, and these subjects have the gift to attract all kinds of nutcases here in the comments section. It would be a shame to pollute the blog like that.

  19. David says:

    My least favorite of your traditional (pre-pandemic) blog topics: layoff updates. Let’s not have any more of those.

  20. Simon says:

    I vote for more odd natural product structures.

    1. Curt F. says:

      Seconded!

  21. GamingBuck says:

    As a layperson I came here first years ago reading an article on Things I Won’t Work With, which I really enjoyed.

    However, I ended up sticking around, even though lots of stuff went way over my head. Thanks, Derek, for putting up with the COVID stuff. I’ve passed your articles on to many people who had legit questions, and view you as a nice, independent, level head throughout this whole thing.

    Finally, I’d like to say (again as a layperson), that I really enjoyed your article on MDMA. It was very approachable to people like me, and I found the subject quite interesting (even though I share your thoughts on recreational use!).

  22. Aleksei Besogonov says:

    If you DO want to read a site that specializes on Whac-A-Mole of anti-vaccine conspiracies, then I highly recommend Orac: https://respectfulinsolence.com/

    He’s writing novel-sized posts debunking anti-vaccine crap.

  23. Tessa says:

    I came to this blog from [I think Hacker News] and it was either TIWWW or Ignition. I then found more to read from a balanced steady hand that mostly asked me to think harder.

    Then once again I got lead back more frequently in early 2020 – probably from Twitter.

    I so look forward to my dip into something I know will test my thinking, knowledge and citical skills.

    Derek I salute you for your firm steady voice.
    [BTW, the sauerkraut was so sensitive to oxygen that I would only recommend the method to perfectionists]

  24. luysii says:

    It is certainly frustrating to deal with antiVaxers, but we should all keep trying. The stakes are too large. You’re trying to save their life. Don’t snark about the Darwin awards. Life is precious.

    As I’ve proposed, simply requiring hospitals to report whether those dying of COVID19 were vaccinated or not should help. Apparently lots of states have reached 50% vaccination. If vaccine efficacy continues to hold, most of the dying will be unvaccinated (if they aren’t already) — as time passes this should change a few minds.

    Also feel free to show them this

    Anti-vaxers, what is it that you know that we don’t ?

    32 members of the University of Pennsylvania Medical School class of 1966 held a 55th reunion by Zoom a week ago. All 32 have been (voluntarily) vaccinated.

    Among the attendees were

    l. Mike Brown — Nobel Laureate whose work led to the statins — https://en.wikipedia.org/wiki/Michael_Stuart_Brown

    2. Jerry Gardner — All American Basketball Player Kansas ’62 — https://kuathletics.com/roster/jerry-gardner/ — but far from a dumb jock — established a GastroIntestinal program at the National Institutes of Health

    3. An (emeritus) professor of neurology at the University of Rochester Medical School

    4. The (emeritus) director of the radiology residency program at Yale Medical School

    5. An (emeritus) professor of medicine at Albert Einstein Medical school

    6. A (retired) Rear Admiral in the US Navy

    There are several more deans and professors among the 32, but you get the idea.

    All classmates who spent their careers taking care of the sick (such as yours truly) were board certified in their specialties. Some were even board examiners for certification in their specialties (such as yrs trly).

    Don’t do as I do, do as I say never works. Anyone who’s raised kids knows that. The Penn Med class of 1966 has put its money where its mouth is.

    So what is it that you know about vaccines that we don’t? Please get vaccinated. The new strain (B.1.1.7) is 50% more lethal and much more infectious than the original pandemic virus [ Nature vol. 593 pp. 270 – 274 ’21 ].

    Addendum 20 May: I thought the following comment and my response were worth placing in the body of the post.

    From DH :The one thing everyone in your sample has in common is old age and thus relatively high risk of death if infected with COVID. A lot of the people I argue with online are not absolute anti-vaxxers, but claim that for healthy people under 30, the risk-reward calculus favors not getting vaccinated (e.g., because the vaccines were “rushed”).

    I disagree with them, but to be fair to them, your class of 1966 example is not an argument that addresses their claim.

    Response: DH — thanks for commenting: I quite agree with what you say, but there are larger issues. My sample is small but I know several antiVaxers in their 70s. The proportion of unvaccinated minorities is larger than their proportion in the population. Many of them live in multigenerational households so an infected 30 year old could kill granny. Just look at what’s going on in India.

    Even worse is the fact that the newer mutations may be more virulent as well as more infectious. This has now been shown to be the case for B.1.1.7 [ Nature vol. 593 pp. 270 – 274 ’21 ]. Even if the vaccines aren’t quite as effective (in vitro) against the new strains, they still offer protection. We will inevitably continue to see new mutants. A vaccinated population is our best hope.

  25. Josh says:

    Your COVID posts have been full of useful information that has really helped me understand the process and what went into these amazing vaccines – even the differences between them. An amazing resource.

    But I’ve been coming here for years to read this anyway, and I’m looking forward to more Peroxides and things that go boom. And discoveries in other areas!

  26. Jonathan B says:

    For what it is worth, I am one who came here because of your informed posts about Covid, and have stayed and joined the discussions on other topics. (I had actually read isolated posts of yours previously by following links, but never bookmarked your site for repeat visits). Can I reassure you, your Covid posts mean much more to me because you clearly have the scientific curiosity to explore critically any new development in disease and therapeutics?

    And also, I share your glass-half-full optimism over Covid. It is completely amazing how in a very short time frame science has created multiple vaccines, all using relatively novel technologies, which have been proven effective in high quality clinical trials. That is to be celebrated! And that while our understanding of Covid is still quite fresh so there may be new surprises in store, so far it looks as if only certain regions of the SARS-CoV-2 spike protein can be mutated in variants if they are to remain viable, and at least part of the vaccine-induced immune response recognises the unchanging sequences. As a result it seem most probable (nothing is certain) that vaccinated individuals will remain partially protected against the variants arising, which in turn means they are unlikely to suffer severe disease. It is just a matter of getting most people vaccinated – worldwide.

  27. Ash says:

    I’m looking forward to more non-COVID posts. Posts about the pandemic are excellent and important, but they just don’t personally resonate with me that much.

  28. theasdgamer says:

    You know, it’s a funny thing. I checked the Johns Hopkins data for my county against my county’s data and there’s a tremendous mismatch. My county health dept. has the deaths from covid peaking late Dec., but the Johns Hopkins data has _huge_ spikes on 01-05-21 and on 01-15-21, which are several standard deviations distant from any other daily death numbers and surrounded by multiple days of 0 deaths.

    Could some of you all check your own county health dept. data against the Johns Hopkins data and report what you find, whether they match or not? Thank you.

    1. Byrel Mitchell says:

      That sounds like one of them is just smoothing the data to remove artifacts and noise.

      1. theasdgamer says:

        I also thought it might be smoothing initially, but then I thought again.

        My county’s data is based on actual reports from hospitals and physicians. I have no idea where JH gets its data for my county. It’s possible that my county health dept. sent a bunch of data on two days. If so, that is concerning because it might lead to misperceptions.

        Could you please check your county’s data against JH?

  29. Philip says:

    As an IT person that worked in research, including pharma for many years I would like to say thank you for all of your posts over the last decade. I have learned a lot. A lot of the posts were over my head, which is good. I like to be challenged.

    I checked to see how many times I have emailed you from my current account. I found 37 emails, mostly about typos going back almost 10 years. Thanks for taking the time to answer them.

    The SARS-CoV-2 posts over the last year or so have been a great source of information. I have not always agreed with some of the policy issues (delayed second dose as an example), but I always respect your knowledge, logic and reasoning.

    Please keep up the great work.

  30. Anon says:

    Can you also not do constant advertising for certain groups please? I mean you don’t have to highlight every other JACS or Nature paper from certain groups. What about useful methods in other journals? Nothing worth talking about? Is med chem or organic chemistry onlydone by superstars?

  31. Byrel Mitchell says:

    To be honest, I drifted away from this blog as I drifted away from compulsively seeking COVID updates late last year. I was pretty burned out, and the course had been relatively stable (at a certain zoom-level) for a couple months.

    Absolutely loving your recent posts on anti-aging and chemistry. I’m no chemist, but your blog helps me understand the state of the field and keep up on the exciting things that happen.

    Thanks for all your writing Derek!

  32. Kai Lowell says:

    I’m another who very much enjoys the recipes, but I’ve also enjoyed the rest of it (especially Things I Won’t Work With) – you have a delightful ability to make whatever you discuss quite accessible to the average non-scientist, and I very much appreciate that!

  33. Kaleberg says:

    I came to read about Exubera, the inhaled insulin that failed.I came back for the posts on chemistry and the pharma industry. As a computer software person, it’s nice to learn that some other fields that are just as full of wonders, nightmares, surprises and gotchas – sometimes all at once.

    Your COVID coverage has been invaluable, and it filled an important niche given that so much about COVID and our response to it was novel. Having grown up in the era of “wonder drugs”, I never expected to live through two great viral epidemics, AIDS and now COVID, both with major societal and scientific impact. The giants of penicillin and the polio vaccine were of the past. Watching a new generation of giants rise up with a new generation of anti-virals and now mRNA based vaccines has been amazing. I consider your blog the definitive chronicle.

    (Of course, now it’s time to get back to the rim of the Exubera Crater and resume your mission.)

  34. rhodium says:

    It seems the readers of this blog should crowdsource funding for groups that do polynitro compounds or things with lots of O-O and O-F bonds or frontiers in volatile Se compounds so Dr. Lowe can write more TIWWW essays.

    1. miles says:

      Or recipes generating excessive flatus

  35. Miesmuschel says:

    Thanks for all the excellent Covid-19 content over the last months. This blog has become one of my major sources on that topic during that time.

    For the record: I initially stumbled onto this blog via the liquid nitrogen cylinder entry in the How Not to Do It category, and I stuck around ever since. So, since your more light-hearted entries seem to be a rather common entry point, you might keep a few Covid readers around by doing one of those from time to time (If you actually want to keep those around, that is).

    Keep up the good work!

  36. Kiss the Chemist says:

    I just love SNAKE OIL posts. Reading Derek systematically and very politely destroy some self-important goon just makes life worht while!

  37. Kiss the Chemist says:

    Oh merde….its worth not worht!

  38. J says:

    Thank you Derek. Your blog is on my regular reading list.

  39. AGMMGA says:

    I came here for the “things I won’t work with” posts, and I stayed because I loved the interesting and insightful posts on everything chemistry and medicine.
    I really appreciated the posts you made about Covid – they were a clear light of rationality in a sea of misinformation. But yes, thanks to science, we are ready to move on from the present pandemic. Time to look to more fun and interesting stuff!
    Thanks for all the posts, no matter the topic, Derek!

    P.S. Nobel prize for medicine 2021 going to mRNA + ADV vaccines. Good bet?

  40. Johnathan Hughes says:

    Another vote here for more things that go boom! 😉

    I have loved the COVID-19 information, and it’s been great for me (and a good resource for helping to deal with fears – my own and those of my friends). However, it’s indeed time to get back to semi-normal. Though the Pandemic will take a while to die, there’s more in the world of pharmacology than vaccines and antivirals.

    Thank you for your work!

  41. Charles H says:

    Proposed topic: This month’s Scientific American cover was about “The coming plague”, and they picked fungi as the danger. What good treatments are being developed for various fungi?

  42. theasdgamer says:

    Isn’t it interesting that the seven-day moving average of the rate of PCR positives for covid cases in the US stopped increasing around December 9th?

    This might not seem obvious at first. The Dec 24–Jan 17 data is obviously concocted by county health departments lumping multiple case days together. There’s a dip between Dec. 23rd and Jan. 4th whose area matches the area between Jan. 4th and Jan. 17th. Cases from the dip were shoved into the area of increase. I saw this in my own county’s data which didn’t match the JH data. The JH data showed multiple days of zero deaths around two spikes on Jan. 5 and Jan. 15. Probably county health departments reported multiple days’ cases and deaths as single days. Why would they do this? To hide the fact that covid had become endemic so that people would get the vaccines.

    https://ourworldindata.org/coronavirus/country/united-states

    It looks like Dec. 9th, 2020 is when covid became endemic in the US.

    But I’m sure that the data shows that the vaxxes were able to retroactively cause this.

    1. JAM says:

      No, it’s not interesting.

      1. theasdgamer says:

        You might find Scott Adams’ cartoons interesting.

    2. NPs says:

      I agree with you that the pandemic is over and the remaining vaccine doses should be thrown in the garbage but please be careful of over-interpreting the PCR case numbers. I’ve heard that the PCR diagnostic test is completely unreliable due to an egregious error in the cycling parameters.

      1. theasdgamer says:

        I am well aware of all your points.

        PCR cannot be used clinically to diagnose ILIs with any assurance _by itself_. Viral culturing _must_ be done in order to have assurance in particular clinical cases. This means that PCR is useless _by itself_ when conducting clinical research involving viral transmission.

        However…

        PCR _can_ be used accurately in public health to check a population’s exposure to a virus. If the rate of PCR positives is increasing, then the virus is continuing towards peak infection. On reaching peak infection, then the rate of PCR positives will no longer increase. After that, the virus moves into endemic status quite rapidly (typically within days), assuming that over 50% of the population has been exposed.

        1. NPs says:

          My sarcasm is no good.

          The points you make are contradictory. Whether its for a clinical diagnosis or tracking for public health they rely on the same test. The overall case numbers that are reported for each county are simply a summation of PCR positive results. So the results are useless when it comes to diagnosing “particular clinical cases” but magically become valuable after compiling those individual cases into an overall population positivity rate for tracking the “population’s exposure to a virus”?

          Eat your cake or keep it.

          1. theasdgamer says:

            Apparently you can’t distinguish between viruses and viral DNA fragments left over from an infection.

            Your “sarcasm” is just bad science.

          2. sgcox says:

            Dear theasdgamer,
            Standard PCR tests employed in US, Europe and I believe rest of the world are made to detect 3 different parts Sars-Cov-2 genome – O1 , S and N sequences simultaneously.
            Random Sars-Cov-2 RNA pieces will be simply ignored.
            https://www.fda.gov/media/136113/download
            It is in fact the curious pattern of S-dropouts (no signal from S while O and N present) in December, caused by 6 nuc deletion in S, led to the very swift identification and tracking of Kent variant in UK. So whatever you believe, PCR tests are very rigorous, sensitive and robust.

          3. sgcox says:

            and BTW, there no DNA fragments ever left after Sars, Sars2, Mers, and four of our old “good” HCoV infections. Now, when I think about it, I did not have a sniff of common cold for last 1.5 years, guess thanks to masks and social distancing.

    3. FFS says:

      Er, delays in reporting caused by the holiday season? Surely not, it must be a CONSPIRACY!

      We have this all the time in the UK, every weekend there’s a dip caused by a delay in reporting of deaths when people aren’t at work.

      1. theasdgamer says:

        So you aren’t contesting my point that covid was already endemic when the vaccines were rolled at?

  43. Cassandra says:

    Convinced of the safety and efficacy… I remain otherwise convinced here’s the latest in a long line of safety related issues:

    https://www.nbcnews.com/health/health-news/cdc-looking-possible-link-between-heart-problem-covid-vaccines-young-n1268319

    Keep needling our youth who are at virtually zero risk from Covid and give them myocarditis! Great idea! Did we learn nothing from Pandemrix?

    The vaccines are so efficacious that the most vaccinated country in the world got locked down again after a “monumentally successful” vaccination campaign – see Seychelles. We find ourselves in a lull period in much of the world, just like we did last summer after wave 1, and many are calling it a vaccine induced victory!!!! Yeah, we are saved! Go vaccines!!! Why are the UK not so cocky, mere weeks after lifting a draconian lockdown imposed since before Christmas!?!?

    Let’s wait and see how well the vaccines are REALLY working, we should know by early to mid-2022. Wait before declaring a triumph and clapping pharma on the back and awarding Nobel prizes. Remember that operation warped speed was the seed of Donald J Trump, maybe an ignobel prize will turn out to be more appropriate.

    The folk who died from their vaccines would also disagree from beyond the grave.
    Thankfully the one sided pro-vaccine drivel will not be spewed so often by Dr D pharma fanboy #1 and his crew of sycophantic followers.

    1. zero says:

      You appear to be a traveler from a parallel universe. For the sake of all involved, I hope you get home safely.

    2. Miles says:

      My friend Keith Sutcliffe I have known for 45 years would have welcomed the vaccine – unfortunately he died last summer of the virus.

    3. theasdgamer says:

      It’s a shame that the medical community has been pressured to not give certain politically-incorrect covid antivirals.

      I’m sure it’s not to eliminate competition to vaccines. /s

    4. Miles says:

      I am afraid you award yourself a moniker far above your station…Cassandra proved to be correct in her predictions.

  44. zero says:

    Personally, I like reading about new tools and techniques since those are often the developments that drive science forward.

    If I could request any post, it would be a discussion of what a biochem lab on Mars might look like in terms of making pharmaceuticals for settlers. What can you do with water, dirt and electricity? What sorts of things simply must come from Earth?

    1. sgcox says:

      Nitrogen source probably. It is certainly there in the same abundance as on Earth but in what usable form ? It is even more important for potential agriculture. Can ammonium production can be done on scale on Mars? Otherwise, forget it.

      1. zero says:

        N2 is about half of the atmosphere once you remove the CO2, with argon as the main remainder. Propellant production will involve a lot of hydrogen, so a Haber process plant would slot in nicely with the already-planned industrial base.

        1. sgcox says:

          You are absolutely right here, zero.
          Now we just need to find a good source of CH4 or similar.
          I frankly have no ideas. May be should simply forget about Mars and go straight to Titan.
          Now, that is very rich of tasteful organics…

  45. Jo Jo says:

    Derek, I love it all, even the parts I don’t understand. I’m an IT guy who has enjoyed the discussions of the various problems you face that seem to be analogs of what I go through. I have enough chemistry/physics background to very much enjoy TIWWW. With some help from my brother (a biochemical researcher with a PhD) I understand some of the topics I might have otherwise skipped.

    Write whatever you like. People who don’t care will skip things, and those of us who want to be challenged and grow will try to read it all 🙂

  46. Stroodle says:

    More gene therapy posts please!

    Also should mention this has been a great stop for reliable information the past year. I first got into your blog back in my med chem PhD days, your ‘how not to do it’ posts are priceless.

  47. gippgig says:

    Derek, I looked at some previous entries and found that none of the errors I e-mailed you about had been corrected. You previously wrote that I was sending them to the correct e-mail address so why haven’t they been fixed? It’s a waste of my limited time to report all these problems if it’s just going to be ignored. Should I stop reporting problems?

    CRISPR Editing in Primates – but these is the first primate numbers – this is or these are
    Your entire bloodstream goes sluicing through the liver constantly; you’re not going to ? able to dodge it
    the team was targeting an adenine residues were near splicing site – garbled
    (with all the appropriate modifications to make it express well – this is very much like making an mRNA vaccine, just with a very different payload. – unbalanced (
    That mRNA and the guide mRNA?
    (albeit with some modifications ? the guide RNA

    Clearing Cellular Dead Wood – But it’s clear that senescent ? have a different secretory profile
    is why they don’t go down some apoptotic pathway and just fall on their on? cellular swords
    That also makes it a bit less of a mighty sword across senescent cell types – for example, it appears that you need that pathway for activity against glioblastoma cells – glioblastoma cells are senescent?

    A Word on Blog Topics – so that if someone finds themselves uninterested in a given post, that they can be pretty sure – delete either that
    few people saw (and I don’t blame them!) – add . after )
    Now, one response to that it? “Well, you haven’t waiting? long enough”

    1. Derek Lowe says:

      I have been working up from your earlier emails, but admittedly I’m quite behind! I appreciate the amount of proofreading that you’ve done (and do), but it’s only infrequently that I am able to work in a session of these corrections. I understand that you devote a fair amount of time to this, and wanted to way that you are certainly under no obligation to keep it up if it’s eating into your own activities (please!)

  48. James Millar says:

    I’m another reader who discovered you via TIWWW, and stayed because it’s all fascinating – I spent a long time reading over old posts, category by category.

    The covid-related stuff has been very helpful and educational, but I am also glad to see more of the non-pandemic content appearing.

  49. DogumGunu says:

    The pandemic process was intense, mentally and physically stressful … This process inevitably overwhelmed us. I am expecting more non-COVID posts from you.

  50. Zambo says:

    Just wanted to say thanks for your excellent coverage over the last year. I’ve always enjoyed science, but am by no means an expert, and I found that by reading your posts (and the comments that went with them) I was well-informed about emerging pandemic/vaccine news, often weeks before big news outlets would even start covering them. I will probably end up being one of the readers that you shed (though I’m sure I’ll still pop back in on occasion, especially if there are any new “things I won’t work with” posts, of which I’ve become quite fond), but I’ll always be grateful to you and your blog for keeping me sane during the pandemic.

  51. Bill says:

    I know it’s already been said by others, and more eloquently, but your blog was a lifeline during the worst, craziest, scariest year+ of my life. Thanks for being a candle in the darkness, Derek. I plan to stick around for the other stuff.

    1. Richard W. says:

      True … but we found out later that Derek was relatively late to be vaccinated … like maybe he wasn’t sure it was safe? If I had known that, I would have probably waited a little longer!

      1. Derek Lowe says:

        I can assure you that I was awake at midnight on the very first day that I was eligible to be vaccinated in Massachusetts, eagerly trying to book an appointment. I had no hesitations whatsoever, and left the CVS where I found an opening with a huge grin on my face after both shots.

  52. ScientistSailor says:

    Just when I think I’m out, they pull me back in…
    Molecular Biology Clues Portray SARS-CoV‑2 as a Gain-of-Function
    Laboratory Manipulation of Bat CoV RaTG13

    https://pubs.acs.org/doi/10.1021/acsmedchemlett.1c00274

    1. Stroodle says:

      Strange that this was published in med Chem letters.

      Firstly:
      “a U.S. NIH funded $3.7 million grant was approved by Trump’s COVID-19 advisor Anthony Fauci in 2015.”

      What? Trump wasn’t president then??

      And then:
      “Strikingly, the two adjacent arginines are coded by two consecutive CGG codons. Only about 5% of arginines in SARS-CoV-2 or RaTG13 are coded by CGG.(3) This implies that the CGGCGG in the inset would have an estimated 0.25% probability to “naturally” occur as an encoder of the RR motif. Other suspicious aspects pertain to the way in which the encoding cassette was inserted to create the cleavage site. The insertion causes a split in the original codon for serine (TCA) in RaTG13,(3) so the TC portion becomes now part of a new codon for serine (TCT), while the terminal adenosine (A) becomes part of a codon for alanine (GCA), yielding the following sequence: TC[TCCTCGGCGGGC]A. This is very odd, clearly pointing to an artificial origin.”

      I’m not sure how random insertions occur, but if I were to make this artificially, I would keep the existing codons intact.

      I would be interested in the opinion of an evolutionary molecular biologist. The author is clearly well published, but this doesn’t appear to be their area of expertise.

      1. stewart says:

        If you look at lots of data you will find lots of low probability events. (Hence a replication crisis in various sciences, and particle physicists adopting a 6 sigma standard.)

        There are a couple of reasons why I’d doubt the probability calculation as well.

        It assumes that the two codon assignments are independent. But repeated codons may arise from duplication due to slippage during replication. A phylogenetic analysis might be able to evaluate this possibility for this instance, but averaged over many genomes I’d expect to see a small excess of identical paired codons. But a difference of, say, 0.26% versus 0.25% isn’t much, so this isn’t an additional refutation.

        It also assumes that codon assignments are random. But codon assignments are constrained by evolutionary history. If you had sufficient genomes sequenced to do a phylogenetic analysis, you could infer the ancestral sequence. The probability of getting a particular arginine codon at a particular locus can be much different from the frequency of that codon within the genome. If the sequence is a “random” insertion into the genome this isn’t relevant, but you have to look at more genomes to tell whether this was a gain in SARS-COV-2 or a loss in RaTG13.

        (Comments made on the basis of quoted text, and not of the whole paper.)

  53. Richard West says:

    When is it safe to forget about Coronavirus and act like it’s 2018 again … and go out and shake hands and hug strangers? It it too soon?

  54. Nytro says:

    More “surviving grad school”, “how to start out in industry” and “state of the job market” posts please!

  55. Russ says:

    Hugs for family and friends, not strangers. Handshaking is probably now a thing of the past, which is a real shame. I would love to shake Katy Kariko’s hand.

  56. Earl Killian says:

    The most interesting blog topics will be the ones you are passionate about because those will be the ones with the deepest investigation. Keep up a fine blog.

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