- I enjoyed this paper, because it plays to my own prejudices. I’ve long believed that assays and experiments should be conducted as close to the real biological systems as is feasible, and that if you are (perforce) starting in more simplified ones, that you should move up the scale as soon as you can. That means if you show up with purified protein assay data, I’ll ask when it’s going into cells, and if you have cell data I’ll ask […]
- Let’s have a look at the unique situation of UniQure. It’s a story about central nervous system disease therapy, that’s for sure. And it’s a story about clinical trial design, and it’s also a story about new and challenging modes of treatment working their way into such human trails. But unfortunately, it has turned most of all into a story about regulatory affairs as they are run under the Trump administration. This is all about a potential therapy for Huntington’s […]
- Here’s a really interesting (but rather unnerving) look at the state of “big data” in biomedical science. The author had been working on some software tools to find copy-pasted blocks of data in large data sets as a method of fraud detection. Such duplications have been the subject of controversy in papers from the SĂĽdhof lab at Stanford (and you can get two different sorts of perspective on that case with those links) and also with the Pruitt lab at […]
- I’ve written a number of posts here about weird natural products (and another such roundup is in the works), but I couldn’t resist highlighting this paper. The compounds discussed (which have been found to be produced in bacteria, specifically one human-pathogenic species, Nocardia ninae) are not huge and bewilderingly complex. Natural products have plenty of those kinds of structures, but these are very small molecules indeed. They’re just really unlikely ones. That’s because they’re diazo compounds – yep, like good […]
- Quick preface: For those who have asked, my in-laws in Iran are (so far) all OK, but we are all of course in an extremely dangerous, stupid, and random situation right now. So yes, it does feel a bit odd to be writing about science and medical topics when there are so many other things going on (and going off) in the world. But this is one way I keep my own equilibrium, and I hope that that word of […]
- Here’s a transcript of a recent podcast over at Nature in their Careers section. They’ve been doing a series on what they feel are taboo topics in the workplace, and previous ones have covered things as disparate as alcohol abuse and religious convictions. This latest one, though hits on a subject that might not sound, to someone who hasn’t been in academia, like that much of a divisive issue. But it is: leaving academia to go into industry. The host […]
- Here’s a real oddity for you in the field of antiviral mechanisms. Over the years people have looked at all sorts of viral infection and propagation mechanisms, trying to find vulnerabilities to exploit. But “cell membrane stiffening” leading to decreased fluidity and impaired viral entry has never, to my knowledge, been one of them. So how to you get that toughened-up membrane state? The authors say that this is downstream of the mechanosensor Piezo1. That’s an interesting system – the […]
- One of the things that seems clear (after many years of writing this blog and fielding questions about drug research from all and sundry) is that most people outside the field don’t realize the failure rates for drug trials. And they don’t realize how often it is that seemingly good ideas just don’t pan out. The recurring proposals to de-emphasize confirmatory trials for efficacy in favor of moving ahead with getting medications to patients is an example of this. Advocates […]
- This perspective is well worth reading, even if you find yourself arguing with some parts of it (here's a freely available preprint version). Longtime drug discovery guy Mark Murcko titled it “The Affinity Advantage”, and I think this gets across the point he’s trying to make: “I argue that a greater emphasis on optimizing binding affinity will accelerate drug discovery. Note that “optimizing” is not always synonymous with “maximizing” So let’s talk about that! As the paper notes in the […]
- There’s been a lot of talk in recent years about “liquid biopsies” and especially about the promise of using blood samples to test for a wide variety of cancers at once. In most cases, this involves looking for fragments of tumor-associated DNA or RNA that are circulating in the blood, and on the face of it, that seems like a pretty good plan. But it has some challenges. One is whether or not a given tumor sheds enough signal to […]
- Here’s a very interesting rundown on an issue that became apparent during the coronavirus vaccine development period. You may remember (if you haven’t expunged that entire period from your mind!) that although the mRNA vaccines were the biggest successes, that adenovirus-vectored vaccines from AstraZeneca and Janssen/J&J were also in the race. But those ran into trouble as they were rolled out into larger populations (I wrote about this here at the time). All drugs (and that includes all vaccines) are […]
- After having just written last week about the FDA’s refusal to consider Moderna’s mRNA vaccine application, the agency has apparently reversed course and told the company that they will accept it. According to Stat, the agency will review the vaccine in 50-64-year-olds via the regular pathway and over-65s via accelerated approval with a required post-marketing study if approved, and has set a deadline of August 5. This is good news right on the face of it, and you have to […]
- This weekend brought news that the Russian opposition leader Alexei Navalny was poisoned in prison by the compound epibatidine. That is not (to put it delicately) the first thing one would have expected, so I wanted to give a little background on this compound first. It’s a toxin isolated from a frog species found in Ecuador and Peru (and a few of its relatives), and like all poison frogs it is a very festive-looking creature indeed. That is of course […]
- Edit: as of February 19, this paper has picked up (rather rapidly) an Editorial Expression of Concern. ". . .concerns have been raised regarding inconsistencies between the registration record of this trial on clinicaltrials.gov and (the) published version (of) the study protocol, as well as with some of the findings in this study" That doesn't sound good so far. The editors say that they are investigating and will report with more details, and I'll add those here as they appear. […]
- I’ve written before a time or two about retroviral DNA, which is something that we’re all carrying around whether we feel like it or not. Over evolutionary time there have been a number of events where human germ cell lines have had these sequences inserted into them by retroviral infection, and we’ve been living with them ever since. Mutations occur, of course, and some of these sequences are rather decayed by now, but it seems that between 5 and 10% […]
- Last night brought news that the FDA has refused to review Moderna’s application for their new mRNA influenza vaccine, and more details have emerged so far today. All of them are infuriating. Right off, let’s just make clear that an outright refusal-to-review rejection like this is quite unusual, since biopharma companies (large and small) typically work with the FDA during their trials to make sure that things are being run in a way that the agency finds acceptable. Why wouldn’t […]
- The list of weird ideas for using bifunctional molecules is nowhere near reaching its end, and this paper is another example of that. There have been scattered reports over the years of small molecules that inactivate particular proteins by causing them to assemble into inappropriate multimeric forms, which are inactive in themselves and/or degraded by cells once formed. The authors here are deliberately aiming at that effect. To do that they target proteins that are known to self-assemble into homodimers […]
- This is a pretty weird idea, but it seems to work. I’ve written many times about aspect of crystallography, but there’s one great big overarching concern in that field that you have to get past: can you even get crystals of your desired compound at all? Advances in x-ray crystallography and electron diffraction have helped to push the size and availability of useful crystals further and further, and we can now get experimental structures from samples that once would have […]
- Here, thanks to Milkshake over at Org Prep Daily, is an example of what the scientific literature is slowly turning into under the onslaught of chatbots. The Royal Society of Chemistry journal Sustainable Energy and Fuels has a paper in it that's been up for a while (published in August of 2024) with the unremarkable title of "Critical insights into eutectic molten hydroxide electrolysis for sustainable green hydrogen production". It's not a topic that I pay that much attention to, […]
- Here’s one that I hadn’t heard of: there is epidemiological evidence that a medical history of cancer seems to decrease the risk of an Alzheimer’s diagnosis. From the looks of it, this observation has survived several attempts to make it go away. That’s exactly how you should treat such an interesting hypothesis, because it gets much more interesting if you can’t easily dismiss it. Very roughly, a cancer diagnosis appears to lower the risk of later Alzheimer’s disease by around […]
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