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Using the Time

I’ve come to accept that the site is going to be pretty much all-corona-all-the-time during this crisis. I’ll try to do the occasional post on something else, but there’s so much news on the epidemic, so much (nearly involuntary!) interest and, not least, so much complete garbage information out there that I feel that those of us with some expertise to offer and some experience in communicating it should step up. And it’s not like I’m doing drug discovery work in my basement, either, sadly.

So what *are* biopharma researchers doing? There are naturally some who are at the antiviral forefront, and they’re staying busy indeed. Keep in mind, though, that it’s the folks up at the clinical end who are busiest now. I’m an early-stage drug research type, so the kinds of things that I’ve spent my career doing tend to bear fruit in. . .several years, which is not the time frame that’s of greatest importance right now. As mentioned before, trying to develop a drug from scratch is *always* going to take years; there’s just too much to be done. So that’s why you see so much work on repurposing existing drugs – those can go right into humans. The next best thing are the compounds from inside a drug company that made it into human trials but were dropped because they weren’t effective enough against their original target or disease. You’ve got a pretty substantial head start on those, too. But that lead diminishes rapidly as you move down the list from there.

But there are a lot of biopharma folks in “work from home” mode, because they do other kinds of research entirely. What if you’re an expert in osteoclast/osteoblast cell culture for bone research, just to pick a completely different field? Or if your company has no anti-infectives research expertise at all? I’m in that situation myself. I’m lending out my expertise wherever I can, and of course I’m also trying to spread information through this site, but it’s been years since I worked in antiviral research in any capacity. Even that was better classified as fragment-based drug discovery than anything specifically antiviral – if you go far enough upstream, the actual therapeutic area becomes less of an immediate concern. I know far more about viruses and about antiviral drugs than the average person that you would find by throwing a tennis ball into a crowded street (hey, remember crowded streets?) but I’ve spent more time in several other fields than I have that one.

One thing that people are doing during this enforced break from the lab and the workplace is to take stock of their current projects. There are always details that you don’t feel that you’re sufficiently up to speed on, papers that you meant to read and didn’t, ideas that you haven’t devoted enough thought to. Time to catch up! It would be a terrible waste of time to come back to the lab and not have a clear idea of what you’ll be doing, because you’ll have plenty of time to plan it out. And outside of your current projects, it’s time to pick up some new skills as well. Ever wanted to (say) learn some Python? Or perhaps learn why some people want to learn some Python in the first place? Get some general immunology details straight in your head? Improve your understanding of statistics? (Pretty much everyone is in need of that one). Ideally, we can all return to our work smarter and more up-to-date than we were when we left. Admittedly, doing a bit of these things will cut into the time spent stress-scrolling through Twitter feeds and the like, but that’s part of the point of doing them as well.

37 comments on “Using the Time”

  1. Christophe Verlinde says:

    Here is a link from the PDB in Europe that summarizes what the structural research community has already achieved: 29 PDBs and 12 Cryo-EM structures.

  2. DV Henkel-Wallace says:

    > I know far more about viruses and about antiviral drugs than the average person that you would find by throwing a tennis ball into a crowded street

    Maybe not in Kendall Square! 🙂

    I’ve been at home for four weeks now and indeed it’s been a pretty productive period due to the inherent change of priorities and access. All that stuff I wanted to read up on has now risen to the top as many of the the quotidian tasks have become irrelevant, postponed, or impossible.

    1. Cambridge bound says:

      Not sitting on I-90 for an hour+ each way has greatly improved my productivity and mood. I hope we see more of a shift to telecommuting once we get through this.

  3. loupgarous says:

    Discovering the joys of domesticity. My wife had her knee rebuilt arthroscopically, and this involves a certain loss of mobility, as she is reduced for the time being to ambulating with a walker. The tight confines of our kitchen means I’m relearning how to cook (most Cajun men can make a decent stew, because that’s what you do with what you shoot hunting or catch in the water trawling or fishing… but I got out of practice over the years, and my wife’s better at that and enjoys cooking, anyway). So, till her knee mends entirely, I’m the domestic help.

    That all started before COVID-19 became such a nuisance. In my time between preparing what ordinarily I ate or helped clean up after, I’ve enjoyed reading about the pharmacology of the quinine derivatives, not to mention Derek’s entertaining recapitulation of how dye chemistry became a new branch of medicinal chemistry (which filled in huge cracks in what I remember from my chemistry education between “methylene blue”, “salvarsan”, and “atabrine”).

    Reading Wired (my wife gifted us a subscription) which is annoyingly socially aware now – in the good old days, it was refreshingly nerdy and asocial. Re-reading Richard Rhodes’ history of the thermonuclear bomb. Sort of stunned no one’s made a miniseries out of that, because the personalities and office politics involved would support at least two soap opera-type TV adaptations, and Rhodes doesn’t spare the drama in his narration. Probably why that book was only nominated for a Pulitzer, while the volume before it, The Making of the Atomic Bomb, actually won a well-deserved Pulitzer for historical writing. But Dark Sun is so very well researched I’ll probably wear the covers off this copy before I’ve memorized it all.

    Twitter takes more time than it should. A couple of novels are percolating in my head, and stubbornly won’t gel into something like coherent prose.

    1. dearieme says:

      The Making of the Atomic Bomb was excellent. I found his book on Energy much weaker.

      1. loupgarous says:

        Of Rhodes’ two “nuclear bomb” books, The Making of the Atomic Bomb really shone. Part of that is the gaze he gave us into the early lives of the people who gave us nuclear physics. It’s a great history book from so many vantages, and really earned the Pulitzer Prize.

    2. cthulhu says:

      “Dark Sun” is fantastic. Rhodes got very lucky on the timing – the USSR had just collapsed, there were all kind of archives open for a relatively short period, and he was perfectly placed to take advantage. I’ve reread it multiple times and it gets better each time.

      1. loupgarous says:

        Dark Sun‘s unbeatable for technical information at the layman’s level on the Teller-Ulam device (the only thing that could make it better is opening a copy of RDD-7 to see when all that knowledge was declassified). It’s also a window into the US and Soviets’ thermonuclear weapon programs we’ll never have again – if only because most of his sources are either dead now, or at an age where memories of the events won’t be that sharp again. It’s almost carping to complain that Rhodes spent so much time drawing horns on Edward Teller, but Teller had some of that coming. It’s more “how large does this loom in the context of what was happening?” My copy’s on my bedside table just now.

  4. Komm says:

    Just an idea to break up the constant stream, how about astronomy and cooking posts occasionally?

  5. Chris Phoenix says:

    What about educating people about policy? Simple numbers: Deaths seem to be doubling every 2.5 days in the U.S., and people die about 3 weeks after infection. That’s about 8 doublings, or a factor of 256.

    We have 452 deaths in the U.S. today. People infected now will start dying 3 weeks from now. Today’s toll times 256 = 115,000 Americans, already inevitably dead.

    If we wait 2.5 days from today to shut everything down, we will lose another 115,000. Waiting 5 days will kill 330,000. The first week – from today – that we don’t all stay home will kill 770,000 Americans, in addition to the more than 100,000 that are already going to die.

    One week from today, only 3000 Americans will have died. That may not be enough to shut down the country.

    If we wait two weeks from today, we will have killed about 4 million Americans. Half of those will die in the last 2.5 days. More than a million deaths per day.

    If we wait until April 9, then COVID will kill 2.4 million Americans on April 30 alone – plus the 8 million dead to that point.

    Please contact government at all levels, do your best to educate them on the math, and beg them to shut us down immediately!

    (Source for the exponential growth rate: 30 deaths on March 12, 452 on March 22. (I get similar numbers counting from the 2 deaths on March 1.) The current shelter-in-place’s are a fraction of the US population. All these calculations assume a working health care system, which we will not have. )

    1. JasonP says:

      Chris Phoenix – did you mean educating people on policy or politics or fear mongering?

      From the data I have seen (CROI) 80% of Covid-19 cases present as mild and only a small fraction proceed to death. Death clearly favors those with compromised immune systems or other underlying medical issues. So wonder if the facts bear out those statistical projections?

      From what I have seen mortality rates are well under 5% over all, but if we assume double that at 10%, then the projection of over 10.4 million deaths would require 104 million people to be infected, nearly 32%. At 5% that would mean 208 Million infected, or 64% of the total population. But many of the densely populated areas have lock-downs in place, NYC, NJ, Philly, CA, etc. So applying assumptions without the convenience of facts tends to distort results and can lead to fear.

      Also, I believe the statement that we do not have a functioning health care system to be opinion and not fact. While social media focuses on the lowest common denominator and highlights outliers, them ain’t the facts. Sad that we have a culture that races to social media for information without apply rational, logic and critical thinking.

      I appreciate Derek for allowing his thread to be hijacked by this crisis as I believe EDUCATION is the clear and correct treatment for that which seems to be infecting more Americans than Covid-19 – IGNORANCE!

      Thanks to the posters who have shared links! That CROI webcast was a real eye opener, the MedCram videos on YouTube also an excellent source of info for those not as technical as this blog attracts. Keep up the good work – some are paying attention!

      1. Chris Phoenix says:

        My numbers extrapolate only from the death rate. I make no assumptions about infection rate (except that we can’t have more than 100% of the population infected).

        We have a health care system now. But under the kind of caseload that’s projected, it will collapse. When that happens, the death rate seems to increase by 5X. My numbers do not account for that.

        A few days ago some state published the numbers on what percent of their population had the bad kinds of preexisting conditions. It was like half of their entire population, higher in rural areas. I can’t find the article quickly.

        Criticize my calculations if you can, rather than calling names.

        1. dearieme says:

          In England the Department of Health is writing to 1.5 million people to tell them that their health puts them at particular risk from the disease.

          The population of England is officially 56 million, as of 2018.

          1. Chris Phoenix says:

            England’s response has not been noted for its overall wisdom.

            The calculation of people at risk in this state was not mine. It was reported as coming from the state health infrastructure. Sorry I can’t find the article.

        2. TJ says:

          But the death rate can’t keep on increasing, it will slow down eventually. Over 80% will recover and hopefully not catch it again, the 0-9 age group has a 0.0xx% death rate…

          Any way I have been trawling through data from the U.K. Office of National Statistics, after a tip off from a doctor… They have weekly death rates, all in nice spreadsheets.

          In the U.K. over the last 3 years,

          In 2017 between January and May 36,225 people died of Respiratory diseases, In the same time frame 161,490 over 75 year olds died.

          In 2018 between January and May 41,548 people died of Respiratory diseases, In the same time frame 172,580 over 75 year olds died.

          In 2019 between January and May 35,416 people died of Respiratory diseases, In the same time frame 159,828 over 75 year olds died.

          In 2020 between January and February 16,708 people died of Respiratory diseases, In the same time frame 74,036 over 75 year olds died.

          These figures may be relevant for Italy, they have a smaller population but an older population! We are told that 99% of the deaths in Italy the person had other, sometimes 3 other potentially fatal conditions.
          I wonder how many of the 5,476 that have died in Italy having tested positive for the Covid would have appeared in these type of figures anyway.
          Unfortunately it is only after the outbreak we will know if the Covid has killed any extra people above the average for this time of year.
          2018 was a bad year and an extra 5,000 people died of Respiratory diseases, this is interesting when compared with the Italian figure of 5-6,000 dead.

          Heading back to Britain, if a reasonable number of sick of over 75 year olds get Covid in this country we can expect that a reasonable proportion of the 160,000 that on average die at this time to have their death recorded as Covid rather than Cancer / respiratory / etc.

          Also if a reasonable proportion of the 30,000 people sick with a Respiratory disease, also contract Covid they also will be added to the figures!

          I have heard that in Germany (they have some pretty good figures) they are not testing those that have died of what appear to be other causes. While in Italy they are testing every body and adding them to the figures! The U.K. are also doing this so our figures should get worse as we pick up many of those that would have died anyway. Looking at Spain’s figures I suspect they are doing the same.

          1. Chris Phoenix says:

            Yes, it will slow down eventually. But if
            – the highest rate of catching it (the middle of the sigmoid, where it’s still exponentially increasing) is at 20% of the population
            – the exponential doubling rate is 2.5 days
            – the overall fatality rate is 1%

            Then in 2.5 days we will have gone from 10% to 20% of the population. That’s 34 million people infected. About three weeks later, if they all get good medical care, 1% of them die. Assume the 340,000 deaths are spread over a week, so it’s about 50,000 a day. That’s 10X the normal death rate from all causes.

            Obviously the health care system will be overwhelmed. So instead of 1% dying, it’ll probably be more like 5%, based on what’s been observed elsewhere. So that implies 250,000 people dying per day for a week, or about 2 million people. Just from that 2.5 day period where it doubled from 10% to 20% of the population.

            Please, please show me where my numbers are wrong.

  6. DrOcto says:

    Social distancing in Denmark has done well in slowing the spread, and when the government sent everyone home they had no way of knowing how effective the measures would be. But I am yet to see any discussion of what the end game is supposed to be, the so called ‘exit strategy’.

    There are three ways it can go:
    1) complete eradication as per China, with 2 week quarantine at border(s) indefinitely
    2) complete total chaos as per Italy, then you’re all done
    3) slow spread of the disease until a vaccine is ready (12-24 months) maintaining a partial quarantine as per Denmark.

    Given the options, if you’re going to shut a whole country down, then there really does need to be a plan for how to lift that quarantine without the disease running rampant once again.

    1. JB says:

      I think there might be another exit strategy:

      4) slow spread of disease until drug treatment is ready that significantly reduces mortality and hospitalisation.

      That’s the one I’m keeping my fingers crossed for!

    2. Some idiot says:

      Just a comment: Yes, the strategy has probably been effective in Denmark (and I think it was the correct one), but just be aware that the public statistics will be misleading, due the change in testing strategy. At a certain point (when the number of cases began to rise sharply), the first of the significant closures (schools, Unis, etc) was put in place. But… At the same time, the testing strategy was changed. Prior to that point, you were tested if you had symptoms and a likely connection to a “risk factor”. After that point, you were mainly only tested if you were hospitalised (plus some other pseudo-random testing at doctor’s clinics in order to gain some information on what the general level in the community is). So, the short version is that the ***apparently*** lower rate of increase after that first Decision Point is likely to be incorrect. The real (or more real…!) number would be coming out of the models, which have not been released. Other experts in Denmark suggest that the real infection rate here is 10 to 90 times higher than the official figures (and this factor would probably also be similar for other lands with a similar testing strategy, of course).

      Will be interesting to see what the situation looks like in 2 weeks time…! Stay safe everyone!!!

  7. Zemyla says:

    Surely there’s some “Things I Won’t Work With” material to be found, like how to disinfect surfaces with chlorine trifluoride.

    1. Hap says:

      I think they use it for cleaning things (silicon wafers), so my first instinct (that you would use it only to disinfect surfaces you never wanted to see again) isn’t correct. Maybe you have other people use it to clean surfaces when you don’t want to see them again, which would make for a very different blog (at least until the police show up).

  8. OnceAChemist says:

    I’ve always wondered what a ‘Things I Won’t Work With’ column would look like if written by a biologist working with infectious diseases. They do it, successfully, but I gotta think that working with lab cultures of ebola or polio or whatever must give rise to the same white-knuckle feeling a chemist has when trying to add that 8th nitro group to a strained ring system.

    1. Iatrochem says:

      along that vein- how about ingredients I wouldn’t cook with?
      or how to write a batch record for gumbo

      1. bks says:

        Bat gumbo?

    2. Simon Auclair the Great and Terrible says:

      Well, I did microbiological work with some fairly nasty foodborn bacterial cultures at the university of Arkansas.
      You get in the habit of sterilizing all the work surfaces and washing your hands as if you had ocd.

      Know what cdo is? Its like ocd but in alphabetical order.

  9. Alan Goldhammer says:

    I have been retired from PhRMA for about 10 years now and pursuing a bunch of other interests. My voice teacher figured out how to use Zoom for my weekly lessons and it seemed to work out well but I do miss the weekly choral rehearsals and our current performance season is probably wiped out. Photography is a bit easier as it’s a solitary activity. I decided to work with all my retired colleagues to track CTs and development papers. I have been surprised by all the pre-prints coming out of China (mainly the Hubei docs and researchers).

    The New York Times ran a nice article a week ago on a large group effort to study the actions between the virus and various cellular proteins. The hope is to identify potential targets that can be addressed by already approved and in trial drugs. the pre-print is now up and they have list of 69 potential compounds: It’s a long paper and takes a while to load from the abstract site.

  10. Matt says:

    I have really appreciated all of the SARS-CoV-2 posts, and the situation changes so quickly I’m sure they’ll continue to be invaluable sources of information.

    One area of recent concern for me has been the recent appearance of unapproved, seemingly un-validated at-home test kits (especially Everlywell). These strike me as even worse than the companies juicing their stock price by touting theoretical vaccines that will never reach development. The companies seem to be operating in a gray space (they often point to the FDA’s Emergency Use Authorization as an excuse for a lack of approval, but that doesn’t excuse the other 30+ tests Everlywell offers).

    1. steve says:

      My understanding from Everly (I contacted them to find out) is that they just supply a kit that you use at home to take a sample and then it goes to a CLIA lab for testing. If that’s the case then I don’t see a problem with it.

  11. JB says:

    Work from home doing regulatory work.

    Taking online courses trying to learn options trading.

    Also, reading this new book by Gerald Posner entitled PHARMA: Greed, Lies, and the Poisoning of America. An absolute must read for anyone in this industry, and absolutely infuriating. Trust me, you know no where near as much about the Sacklers as you think you do. Pharma and it’s lobbyists (ahem PhRMA) have used the same rehashed excuses for drug prices since the 1950s along with collusions for price fixing in the 1950s. Who knew at one point major pharma firms were wire tapping high ranking politicians and other CEOs to get inside information? Corporate espionage at its finest. A must read when people this day in age are dying because they can’t afford insulin. The history of the pharmaceutical industry is truly appalling.

  12. Another Guy says:

    Thank you Derek for continuing your column in these difficult times. Now more than ever we need good evidence-based information and continued debunking of “fake news” to win the war on COVID-19.

  13. Alia says:

    Lucky you. I’m trying to do a crash-course in online teaching and think of the way to keep my students educated, not to bore them to death and manage all technical problems that might arise when most of the country suddenly tries to do everything online at the same time. Yes, I might come out of it with some new skills (like using Microsoft Teams – Microsoft has been kind enought to offer it free of charge for all educational institutions) but since I have about a week to get everything ready, I’m stressed out of my mind.

  14. Anonymous says:

    What are other smaller biotechs or start ups doing now that the governor has asked non-essential employees to stay at home? My boss seems to think we’re exempt, but reading the state announcement I don’t see how we qualify. We’re early discovery for oncology, not doing anything covid-19 related. He wants us to come in as shifts but I’m not sure I’m comfortable with this.

  15. Daniel Jones says:

    Yeah, COVID-19 is gonna dominate. I feel for you, but I also appreciate one of the guys I trust the most on these issues slogging through.

    I should mention; I lost my Mom just a few days before her birthday in January. When he had had her gall bladder removed some years previous the doctor had left instructions without explanations or follow-up and my mother had had a glass a wine or two each day seeking the purported heart benefit.

    As the wincing readers may well guess, she developed Cirrhosis of the liver and that vagueness and lack of follow-up led to our not getting it diagnosed even close to being in time for a transplant. My liver is actually compatible and I would gladly have given a portion. I’d have been honored. But this did not happen.

    All the above is just me finally venting my frustration at a rotten and ostensibly avoidable loss. The stages of liver failure are pretty heartbreaking, to be blunt, and I guess I needed to finally put fingers to keyboard on this.

    What I came to say about Mom is that all the above aside, she would have been hideously at risk from the COVID-19 virus as she had smoked as a young woman and quit in her mid-life. She was still prone to recurring seasonal respiratory hassles from various mold spores and any chest cold would present as low-grade pneumonia. The novel COVID-19 would have killed her, I’m almost certain.

    I mention this as every former smoker, every respiratory allergenic, everyone with a lung/trachea problem of any kind needs to be *extremely* careful during the coming crisis. Plan ahead and assume you’re going to have problems; I wish all of you the very best.

    Good Luck.

    1. Daniel Jones says:

      “when she”… why do you never see the horrible typo until you’ve hit Post Comment?

      1. HU says:

        If that makes you feel any better, my native language does not have gendered pronouns and seldom even uses pronouns, except for pointing (this/that/they).
        I just glanced right over it.

    2. loupgarous says:

      Childhood asthma, bronchitis, and smoking till the age of 30 left me with some pulmonary deadspace. I’m aware of what risk stratum that places me in long before radiation therapy for cancer did its thing for my immune system.

  16. Susan says:

    I think many readers of this blog could make useful contributions to the fight against COVID-19 from home. There’s a consortium of researchers from Spain, Portugal, Argentina, and several other countries who have established a coordination network for tasks that can be done by volunteers to help researchers:

    Some of it is clerical work, and some is high-level biomedical stuff. As a plant ecologist and a single mom who has suddenly transitioned from classroom teaching to dumping everything online, at the same time as losing my childcare– full-time caregiver to a two-year-old all day, full-time online professor all night– I don’t have much to contribute to the fight. But you all do. And you should.

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