- by You get widely varied perspective on targeted cancer therapeutics depending on where you get your information from. Cancer therapy centers in the US like to advertise as if they can zero right in on a particular patient's particular sort of cancer and then reach up on the shelves to pick out which of the thousands of alternatives will be most efficacious. Now it's true that we can do more of that than we used to, but the real-world situation is […]
- by It's safe to say that most people hadn't really heard of lipid nanoparticles until the advent of the mRNA-based coronavirus vaccines. I don't mean to imply that they have a huge profile in the public consciousness, but a lot more people are aware of them who aren't actually formulation scientists. The idea behind these species is that they form very tiny capsules/aggregates that can carry sensitive cargos (like modified mRNAs) without exposing them to degradation in the bloodstream. Moreover, the […]
- by If you don't know anyone who does research on (or using) yeast, you might not have heard about this problem. But for several years now, there's been an annoying and expensive problem for those labs that do depend on yeast cultures: sometimes the yeast die for no apparent reason (or just fail to grow in the first place). Here's an article at Science, and if you look around, you'll see plenty of evidence. For example, here's a supplier of lab […]
- by I wanted to be sure to mention the results of this competition, announced earlier this year. The organizers (Leash Bio) focused on three protein targets (BRD4, EPHX2, and good ol' bovine serum albumin), and they provided assay data from a series of DNA-encoded library screens on roughly 133 million chemical species against these. These were mostly trisubstituted triazines, a classic combinatorial chemistry motif, with some other structures (from a kinase library screen) thrown in for seasoning. Participants were challenged to […]
- by I really hope that the plan described here works out and that it becomes more popular. The ERROR project (Estimating the Reliability and Robustness of Research) is going to pay people to review high-profile papers in psychology looking for errors in code, statistics, and citations. Participants will get a payment for every paper they review, with bonuses for each error caught (and those pay out on a sliding scale of importance). There are 100 planned over the next four years, […]
- by OK, we know that cells transcribe DNA into messenger RNA, and that these mRNAs (after some processing) go on to be translated into proteins by the ribosomes. But how does a cell know which proteins it should be making, which genes it should be transcribing at any given time? And how does it know how much protein synthesis it should have going at all? The only answers that makes sense are networks of feedback loops, and this new paper provides […]
- by It's long been known that many types of tumors exist under relatively low-oxygen conditions. Some of that is due to their own growth – the middle of a large zone of newly grown tissue is likely to be poorly vascularized, and that's really the only way that oxygen can be delivered. You see all sorts of adaptations to this, but make sure to view them from the correct end of the problem. It's not that tumor cells are craftily coming […]
- by In this post, I will not discuss the personal life or behavior of Robert F. Kennedy, Jr. I am speaking only of his scientific and medical opinions, which I was willing to ignore while he was pursuing his hopeless campaign for the presidency. But now that he has dropped out of the race, endorsed Donald Trump, and has been added to Trump's transition team to prepare for his possible re-election to the presidency, it's worth revisiting the topic. I have […]
- by Now this is a very weird preprint, but it looks like the authors have done a pretty thorough job on it. It's about absorption and fluorescence in peptides, which (depending on your perspective!) might sound like a very dry and uninteresting topic, or one that's certainly of interest but has been pretty well worked out over the years. After all, we've been looking at peptides and proteins spectroscopically for decades now – their ultraviolet absorption and their fluorescence (intrinsic and […]
- by Here’s something that you probably don’t think about much unless you’re in the drug scaleup and manufacturing business: mass balance analysis. I’ve never had to worry about it, because I’m so far back up the early-stage discovery organization (and have been for my whole career). I’m fond of saying that there are two yields in medicinal chemistry, Enough and Not Enough, and to a good approximation it doesn’t matter much how much material I started with if the end result […]
- by Well, we were just talking the other day about how many tumors are a low-oxygen environment, and the adaptations that go on because of this. Tumor cells often switch to anaerobic metabolism, while at the same time trying to bring in new blood vessels (for oxygen, for nutrients, for disposing of waste products, etc.) This angiogenesis has long been a target for anticancer drugs, of course, with a particular burst of hope in the early 2000s around the work of […]
- by I've had a number of people write to ask me about my opinion of some recent publicity around the "Four Thieves Vinegar Collective", a proclaimed anarchist group that makes a big deal out of "DIY pharmaceuticals" and the "right to repair your own body". For what it's worth, I wrote a post about these folks a few years ago, and I stand by the opinions in it. I find so much of what these folks have to say to be […]
- by For many months now, several large pharma companies have been negotiating with Medicare about pricing for a list of widely used drugs. This is all pursuant to the Inflation Reduction Act passed in 2022, and the idea is that this is going to happen every year with a fresh list. The companies involved are not happy about doing this – in fact, while they've been negotiating, they've been vigorously fighting the entire idea in court, although to little avail. But […]
- by The BIOSECURE Act (which I last wrote about here) seems to have just passed a House of Representatives vote yesterday, even after a brief news flurry about one or more members who had decided to vote against it. The vote was 306 to 81, which is pretty decisive, especially under current conditions in the House (although to be sure, almost all the No votes were from Democrats). (Update: I see from Steve Usdin's article in BioCentury that two of those […]
- by I enjoyed this paper because it ties together some topics that you would never imagine have any connection. It's about the protein collagen, which is the most abundant one in humans and in many other higher animals. Structurally, it's a triple helix with a lot of prolines and hydroxyprolines, and it's used for a lot of structural purposes. Tendons are the most well-known example, but collagen is found in muscle tissue, the walls of blood vessels and other organs, inside […]
- by Chimeric antigen-receptor T cell (CAR-T) therapy has been an amazing story overall. People had been trying to turn T cells against various sorts of tumors for a long time, because they're pretty fearsome when they're engaged, but attempts kept coming up short. That was due to lack of knowledge about the (extremely complex) landscape of T-cell activation and function, but that gap finally closed in 2011 with the dramatic recovery of a patient who was weeks from death from leukemia. […]
- by This is a fascinating article from Jeffrey Flier of Harvard about research done in the late 1980s and early 1990s on the now-famous GLP-1 therapies. He was involved in a startup company that had a development deal with Pfizer in this area, and the article is a detailed look at how the company went under as Pfizer dismissed the idea of GLP-1 injectables for diabetes (let alone any ideas about weight loss in a nondiabetic patient population). The team had […]
- by There's been some interesting news on the pharmacological-interventions-in-aging area. This new paper reports a trial of metformin in aging male cynomolgous monkeys (13 to 16 years, roughly 40-50 year old by human standards). A treatment group got 20 mg/kg metformin for over three years (roughly ten years of human lifespan) and these were compared to matched control animals of the same age (and to both much younger and to middle-aged cynos as well). The results seem to have been pretty […]
- by Well, since I was talking about CAR-T therapies here the other day, I wanted to highlight this new paper in Cell. Unlike that other post, though, this one has nothing to do with oncology but rather with the rapidly expanding field of using these modified T cells for severe autoimmune diseases. Earlier reports showed remarkable results in patients with refractory lupus, and that same team published follow-up studies earlier this year in these patients along with others who suffered from […]
- by I wish that I shared Alex Tabarrok's optimism here. He says that "AIs with access to vast databases of genes, proteins, networks and so forth will enable new simulations and learning as has already happened with protein folding", and I can see where that might be an attractive prospect. But there are some major problems with it, in my view. I've made some of these arguments sporadically in other places, but I'll try to put them all together here, with […]
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