- by Here’s a look at a source of experimental variability that some chemists might not have considered: magnetic stirring bars. For the non-chemists in the audience, these are a standard bit of lab equipment – they’re just small magnets encased in (typically) a polyfluorocarbon (Teflon) coating. You drop one into your reaction flask and then put them over a “stir plate”, which has a rotating magnet of its own. And this causes the stir bar to spin inside the flask in […]
- by There are still a surprising number of drugs in the "Well, they work but we don't quite understand how" category. Next to that one is the "Well, we know one way that they work but they're clearly doing other things that we don't understand" category, which is even larger! It looks like one of these has finally been cracked, the thiazide diuretics used for treating high blood pressure. These were discovered back in the 1950s, and you can read the […]
- by Here’s an editorial by Adam Feuerstein at Stat that points out that in all the uproar about the Trump administration’s attacks on the NIH (and the NSF, and NOAA, and other science-based agencies), there’s a conspicuous zone of silence. And that’s the biopharma industry. It’s clear that almost everyone is keeping their heads down in the interest of “keeping lines of communication open” and so on. “Thanks for checking in. Nothing to share on this now,” a PhRMA media representative […]
- by I've written a lot around here about the use of ML/AI techniques for antibody design, and it's no wonder that a lot of money is being poured into this area. Proteins in general are riper territory for in silico design than small molecules (as witness the early successes of AlphaFold and RoseTTAFold), for a number of reasons. Chief among those is the way that we were able to train the models against a very large, very well-curated data set of […]
- by (This is part of a series of posts on the attacks on science and federally-funded research in the US. Part III is here). As many will have heard, the last few days have seen even more turmoil in the NIH and other federally funded science agencies. No one should have any doubt by this point: this is an unprecedented situation. There's no "Well, what was the result last time this happened", because there has never been anything to compare to […]
- by It is impossible to say how many human lives have been saved by antibiotics, and there are still a few people alive who lived through the introduction of things like penicillin and sulfanilamide. The dramatic change in the treatment of bacterial infection during that era really can't be overstated. Doctors knew exactly what a terminal infection looked like, because they saw such things frequently, and they knew that there was nothing they could really do about it. Until the advent […]
- by Note: I honestly planned to write about something else today. But as I seem to be saying a lot these days, here we are. . . I wrote here a week ago about the near-total silence from biopharma CEOs about what has been happening under the current administration, and called on people to speak up. We're starting to see some of that, such as this editorial by the CEO of Recursion Pharma. Chris Gibson says (correctly) that basic research funded […]
- by After that post on bacteria and antibiotics the other day, I thought I might give equal time to the antifungals. It's really hard to say which of those fields is harder to make headway in! As I've mentioned before around here, the continued use of as nasty (and as old) a drug as Amphotericin B really shows how much we need new drugs against fungal infections. I think it's safe to say, though, that the tools available in that research […]
- by Here's a new paper addressing something many of have wondered about. The clinical trials of Paxlovid (nirmatrelvir/ritonavir) showed reduced hospitalization and severe coronavirus among the unvaccinated patients studies, but the effect was not significant among vaccinated ones. But in those trials the median ages of the participants were in their 40s, and it's also been very clear that risks for severe disease increase with age. So what is Paxlovid's effect in older populations, and how does that correlate with vaccination […]
- by (This is part of a series of posts on the attacks on science and federally-funded research in the US. Part IV is here). Here is the text of a letter sent to all NIH staff this morning from the acting director, Matthew Memoli. I do not find it as reassuring as I believe he is hoping it to be, but I'll let people draw their own conclusions: Dear Colleagues: I want to acknowledge the challenges we are facing at NIH […]
- by Neurodegeneration is a topic that we simultaneously know a lot and a little about. In some of these conditions (like Huntington's) we have strong evidence of the fundamental abnormalities at the genetic and protein level, while in others (like Alzheimer's) the arguing continues at a high pitch. But in all of them we have problems tracing exactly what's going wrong, and in what order. Working with brain tissue in advanced cases of such degenerative diseases is like coming suddenly upon […]
- by I've been writing about this story for a couple of years now, so I wanted to follow up with the latest news. A team at Sloan-Kettering, BioNTech, and others has been trying to make the long-sought "cancer vaccine" idea a reality, and if anyone thinks that this is a new idea or a sudden overnight success, think again. Immuno-oncology has been trying to get off the ground for decades now, and a lot of "let's attack cancer with the body's […]
- by (Part I is here, and Part II is here. But now we're faced with a whole new issue. . .) Late on Friday came the unexpected and unwelcome news that the NIH is trying to cut the overhead payments in its external grants. If you’re not part of this ecosystem, that might sound like a pretty dull accouncement, but unfortunately, it’s anything but. If they manage to follow through on this (see later in this post for more on that), […]
- by This is part of a series of posts on the attack on Federally funded research and development – Part V is here. Biocentury has an example – and there are many – of what the insane turmoil inside the US government is doing to agencies like the FDA. Speaking with a source who's a reviewer for orphan drugs, they note that there is an ongoing exodus of the staff who handle rare disease approvals, which is the sort of specialized […]
- by This post is part of a continuing series – Part VI is here. I’ve been planning a post like this one, where I address how. . .unusual. . .the site has been lately, with all the updates on government actions, judicial proceedings, and various loud statements about current affairs. But I’m not the only person who usually writes about something else who has been pulled into these issues, and Mike Masnick’s recent post at Techdirt really does a great job […]
- by Now here's a topic that I don't think has come up here before. There are a number of different living creatures – but not us – who can sense magnetic fields, and they use the Earth's intrinsic geomagnetic field as a navigation aid. This has been seen in bacteria and other microorganisms all the way to birds, who use the magnetic field to do their long-range migrations. You can even see disruptions in bird locations after a big sunspot-induced geomagnetic […]
- by I mentioned not long ago that I was looking forward to seeing how Beam Therapeutics would do in their clinical trials of single-base DNA editing therapies, and this morning we have a readout. This was a trial to correct alpha-1 antitrypsin deficiency (AATD), which is a genetically based condition involving a mutation in the SERPINA1 gene. The alpha-1 antitrypsin is a protease-inhibiting protein that blocks the activity of the neutrophil elastase enzyme – that's a mechanism you see in some […]
- by There's been an interesting collaboration for the last several years between the Myers lab at Harvard and the Polikanov lab at Illinois-Chicago on new antibiotic ideas. In 2021 the team reported a variation on clindamycin, dubbed iboxamycin, which I blogged about at the time. Last year they revealed another compound in this series, cresomycin, and now they're out with another paper moving the story along even further. The structures are shown at right, and if you look up clindamycin itself […]
- by I mentioned in January that another clinical trial I was looking forward to seeing read out was the bifunctional estrogen receptor degrader from Arvianas, ARV-471 (vepdegestrant). That's widely regarded as a first major clinical test of a PROTAC-style degrader, so let me spend a paragraph or two going over once more what the heck those are. Skip ahead if you're already a Bifunctional Kind of Person. The idea behind these odd-looking molecules is to hijack an important pathway inside cells […]
- by Here's a paper from the Fujita group at the University of Tokyo that follows up on a long-running project there: getting X-ray crystal structures of compounds without crystallizing them at all. They first reported this phenomenon over ten years ago (time flies!) and it works by soaking the molecules of interest into metal-organic-framework (MOF) crystals. Under the right conditions, the guest molecules line up inside the vast coordination cage of the MOF crystals in such a regular fashion that when […]
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