I read an article in the Guardian titled Scientists find way to slash cost of drugs with some interest; one of the opening parts,

Improvements they devise to the molecular structure of an existing, expensive drug turn it technically into a new medicine which is no longer under a 20-year patent to a multinational drug company and can be made and sold cheaply.

sounds pretty much like the well-known and often cheeky practice of busting drug patents by trying to find a gap in what’s covered, or using a bioisosteric replacement to move outside the patented area, and then developing and patenting a compound of your own in that gap.  Essentially you get to leapfrog over the work done by the first group, hopefully arriving at a working compound without having to go through the expense of a full research project.  In the article’s case this doesn’t seem to be the method under discussion; a quick google around for the scientists involved turns up their company (I’m surprised that it wasn’t actually named in the article), which seems to be based on sticking PEG on proteins (which I would guess is done to improve their bioavailability).  Fair play to them with their technology, but comments like this:

Professor Shaunak says it is time that the monopoly on drug invention and production by multinational corporations - which charge high prices because they need to make big profits for their shareholders - was broken.

Are just plain wrong.  Developing drugs costs a lot of money because, frankly, we’re shit at it: we start with tens of thousands of chemicals and gradually narrow it down to one that enters clinical trials (i.e. actually makes it as far as being given to a person).  Given that only one in five drugs makes it through this stage, the price of which can run into hundreds of millions of dollars, there are a lot of expensive failures along the way.  (I got that one-in-five stat from this article, which is admittedly someone from the pharma industry saying that intellectual property is a good thing.)  This failure rate has sometimes led to a rather risk-averse stance where companies only spend a money on a particular disease/target once someone else has shown that it is possible to produce a drug in the area; the follow-on drugs are often called “Me too” drugs.  The final price of a drug incorporates the cost of research performed by the company, so using other people’s work to jump-start your own is an obvious way of saving money.

Putting this together with the article’s topic, I take the article to say that the company will be putting PEG on existing compounds, thus moving them outside the original compound’s patent and allowing them to produce the final compound at a lower price.  But someone still has to come up with the original compound for them to use, and they’re going to be annoyed if they lose all their profits and so will come after infringers with rabid patent lawers, which will cost a lot to defend against.  Plus I wonder how friendly the FDA will be to this approach; any significant change to a compound usually triggers a new clinical trial, so you still have to go through that huge expense.  That’s alluded to in the article:

Once the drugs have passed through clinical trials and have been licensed in India, the same data could be used to obtain a European licence so that they could be sold to the NHS as well.

No mention of America, so I infer that they’re avoiding the FDA.  I wonder if they’re saving money by doing the trials in India; out-sourcing is certainly a model that’s getting a lot of attention in the pharma industry.

To be honest, I think the main thing that rankles is their claim of being “ethical.”  It’s no more ethical than any other industry where cloning and reverse-engineering exists; Behringer effects pedals are an example that spring to mind, and there was at least one law suit flying around when they came out.  As ever, it’ll be in the hands of the patent lawers as to whether or not this idea will bear fruit.

One for the scientists again, I’m afraid.  I’ve been reading In The Pipeline for a while now, which is a well-written chronicle of the life of a medicinal chemist plus other matters of interest in the pharmaceutical industry.  He’s dealt with polonium posioning, a post on a new twist to RNA interference that makes a nice pair with one on Merck’s acquisition of Sirna, and something that I’ve laughed about before, the crap names of biotech and pharma companies.  Recently the author has been made redundant, which is something I have in common with him; the company I work for went breasts-skyward a few months ago, but I have potential employment with a company that is spinning out from the wreckage.  Of course, in contravention of the naming rules suggested in Lowe’s post, the new company’s name ends in an “X”; hopefully people won’t mind the cliche.

Another chemblog I’ve been keeping an eye on is Totally Medicinal, which is usually posts centred on recent publications in the chemistry literature, plus other synthesis highlights.  It’s definitely a case of a good writing style rescuing what could be quite turgid subject matter; for example, in Feeling Aroused?, TM writes

In BMC (2007, 15, 142-159) Pfizer are riding to the rescue of the sufferers of FSAD - that’s Female Sexual Arousal Disorder. [Stop sniggering at the back there!]. Far be it for me to suggest that this is in fact a bullshit, totally made-up, non-disease. Nothing to do with the fact that loads of people will want to buy these pills and make them loads and loads of money, even if they are only intended and approved for use in a very small subset of patients with a specific aetiology. This is a serious disorder, which demands serious medical attention.

I am looking forward to seeing the spammers latching onto this as soon as a compound makes it to the market.  And it’s rare to see a chemical series described as “a bit gash” in the literature.

Drosophila geneticists have always amused me.  They do lots of serious work developing models of human diseases and teasing apart the complex interactions of genes that happen throughout the lifecycle of the fly, then when the time comes to submit the paper they sit around and see who can come up with the worst pun describing the mutation; there’s a list of some of the best ones here.  There’s one particularly important one for my day-job’s purposes in there: the human homologue of the fly ether-a-go-go gene, hERG, is the new hot anti-target in drug discovery; if your promising new compound blocks hERG it’s not going anywhere near the clinic because this activity is associated with adverse cardiac events.  Human gene names are usually more utilitarian, e.g. BDKRB1 (bradykinin receptor 1), MAPK14 (MAP kinase 14, or more commonly p38 alpha, so named for its molecular weight), KCNA1 (voltage-gated potassium ion channel 1… and even that’s a homologue of the Drosophila shaker gene; guess what the mutant does?).  There are rare outbreaks of humour: the human homologue of the Drosophila gene hedgehog is called sonic hedgehog.  Of course, if any of these genes turns out to be disease-related, this can lead to some interesting patient-doctor discussions, a subject that is currently a hot topic over at HUGO; should potentially offensive gene names be changed?  The obvious answer is yes, for the patients’ sake, but this generates a headache for people researching the area due to the proliferation of synonyms for what is essentially the same thing, albeit in different species.  This is already complicated enough, because usually about three different groups find a gene at about the same time and each will independently name it and proceed to publish papers about it for several years using the name they made.  Eventually one will win out in a betamax vs. VHS stylee (rather than after a knife fight at a conference), but there’s still all those early publications out there.  At a push everything could stay as it is and clinicians can just use the gene symbol when discussing the disease - I doubt everyone with a mutated Ras gene is told that they have a mutation in their Harvey rat sarcoma viral oncogene homolog.  However, I’m sure that having to hide information from patients is not a good thing, and these days the first thing everyone does with a disease is look up more information up the internet, so they’re going to spot any comedy Drosophila homologues anyway.  This would mean that perhaps the fly guys and gals should choose less potentially offensive gene names.  I’m not sure what conclusion to come to here; personally I’d mourn the loss of a little corner of silliness in science, but with all this information now being freely available on the internet it would perhaps pay to be a bit more circumspect.  Though somehow the idea of having a mutation in one’s lunatic fringe does lend a certain levity to disease…

The Tritone Effect is an interesting page demonstrating an audio illusion, which is the audio equivalent of the Necker Cube.  (On a side note, the psychology course I took in the second year of my degree had a brilliant Necker cube practical - the demonstrator handed out glow-in-the-dark wireframe cubes, then turned the lights out.  Holding the cube, we rotated it left and right; all was fine.  Then we were instructed to force our eyes to choose the other interpretation of the wireframe, so the front and rear faces were perceptually reversed.  Now when rotating the cube left, your eyes told you it rotated right, and vice versa.  This made your arm feel wrong.)  The tritone effect is based on Shepard’s Tones (that link is to another page on the same site).  Here’s an explanation:

Although pitch discrimination cues have been carefully removed from Shepard’s Tones, proximity information remains. Two consecutive tones are always separated by a single semitone. So although you can’t really determine which is higher based on the tones alone, your choice is that the second tone is either one semitone higher or eleven semitones lower in pitch than the first. It is natural for the smaller distance to be automatically selected.

In the case of Shepard’s Tones, what would happen if the proximity cue was removed? In other words, what would you hear if the second tone played was either half an octave higher or half an octave lower than the first? (The midpoint of the octave is called the tritone, hence the name of the current illusion.)

What tickled me is that I experience the 110Hz illusion in the opposite way to what most people hear, so I think tone 1 is lower than tone 2.  I also can’t do what Kyla could, which force myself to hear it the other way around.  Besides being further evidence that I’m weird, the illusion is mainly of interest because apparently it is very repeatable in a non-time dependent manner; the way you hear the illusion today is the way you’ll hear it in a year’s time, which would indicate that everyone has perfect pitch.  Perhaps I’ll find some freebie ear-training software and see if improving my pitch recognition turns out to be useful.

blog.tenderbutton.com is the weblog of a (nearly finished) chemistry PhD student… well, it was, because he’s actually just pulled the plug on it.  But anyway, it’s quite interesting in a science geek kind of way; I work with chemists on a daily basis, and need to understand them and their work, so it’s even kind of educational for me.  However, this is something that can be related to by anyone who has ever stuck their finger in their ear.  And (found via various links in another article) this is the most spectacular lab accident I’ve ever heard of.  (Spotted via In The Pipeline.)

Waste money on expensive computational modelling of molecules?  Don’t!  Balloonmolecules will save you time and money (well, maybe just money), and interest a whole new generation of kids in chemistry at the same time.  Check out the model of DNA at the bottom of the gallery page; awesome.

Between this and the old curry fights cancer story, by rights I should be immune to cancer.  Sadly it probably means that I’ll die of liver failure and dyspepsia instead, but you can’t have it both ways.

But don’t rush out to stock the refrigerator. Xanthohumol, is present in such small amounts that a person would have to drink more than 17 beers to consume the same amount found effective in the study

Damnit, there’s always a catch.

After a brief discussion over lunch about what’s denser than lead (yes, we are scientists; sometimes we talk about football, but often we slip and end up talking about geeky stuff), I turned to my favourite source of background information, Wikipedia. Yes I know it can often be badly written or just plain wrong, but I have found it a useful source of historical information, e.g. on the break-up of Yugoslavia or the formation of the state of Israel. In addition it’s fun to follow links around with no real idea of where you’re going to end up. So this lunchtime I started with depleted uranium, which I knew was denser than lead, moved on to Tsar Bomba, the most powerful bomb ever tested by man (with an output at detonation 1% that of the sun), which was designed in part by Andrei Sakharov, whose name was familiar to me for some reason, perhaps because he was one of the people who first came up with the idea of a tokamak design of fusion reactor. It was there that I learned that the reason a tokamak is toroidal is because this shape facilitates the creation of an irregularity-free magnetic field, for reasons explained by a mathematical problem referred to as hairy ball theorem. It is this theorem that gives us a wonderful truth: you can’t comb a tennis ball. From depleted uranium to combing hairy balls in one glorious info trawl. Time-wasting has never been so educational.

I just read an interesting article over in the Guardian by Ben Goldacre, who writes their Bad Science column, entitled Don’t Dumb Me Down. (I’ve no idea how I’ve managed to miss the Bad Science column until now, as I read the Guardian… maybe it’s only in the weekday editions that I rarely buy, or possibly it’s far enough back in the paper that I’ve lost interest by that point. If you’re interested there’s an archive of his articles over at badscience.net, which also has this wonderful bio:

Ben studied Medicine at Magdalen College Oxford where he also edited Isis, the Oxford University Magazine. He left in 1995 with a First: before going on to clinical medicine at UCL, he was a visiting researcher in cognitive neurosciences at the University of Milan, working on fMRI brain scans of language and executive function, and was also funded by the British Academy to do a Masters degree in Philosophy at King’s. He is, as you can see, a serious fuck-off academic ninja.

Anyway, back to the point.) The article sorts bad science reporting into three categories, wacky, scares and “breakthrough” stories, then makes the point that it is the simplistic way in which science news is reported that is really at fault.

Because papers think you won’t understand the “science bit”, all stories involving science must be dumbed down, leaving pieces without enough content to stimulate the only people who are actually going to read them - that is, the people who know a bit about science. Compare this with the book review section, in any newspaper. The more obscure references to Russian novelists and French philosophers you can bang in, the better writer everyone thinks you are. Nobody dumbs down the finance pages. Imagine the fuss if I tried to stick the word “biophoton” on a science page without explaining what it meant. I can tell you, it would never get past the subs or the section editor. But use it on a complementary medicine page, incorrectly, and it sails through.

I’d say it’s a bit of an unfair comparison; an exciting science breakthrough is actually news and so is expected to be read by a wider audience than a book review, which is usually only looked at by someone who’s interested. The dumbing down of science reporting is obvious and I even caught it in action recently. I can’t remember the exact scare story, but I believe it was some work showing a link between leukaemia and living near powerlines. On Radio 4 it was reported as being based on a very small sample set and the actual risk being very very small indeed, and that these two points were clearly made in the paper. By the time it made it to Radio 1, all these caveats had been lost. The main reason for this kind of thing happening is perhaps a more general problem with the media, in that they’ve realised that to sell papers/advertising time they must entertain or shock their audience. Well reasoned, balanced, arguments, which most science consists of, isn’t exciting. Cf the political media in America; fat obnoxious opinionated people make better entertainment than anyone trying to see both sides of an argument and admit that no answer can be completely correct.

I’ve banged on about this before, but now it looks like a team has managed to extract stem cells from a cloned human embryo. As discussed in the New Scientist article, it doesn’t bring reproductive cloning any closer, just the potential for new therapies for e.g. Parkinson’s and diabetes (no idea about why NS have listed autism as a potential benefitor of this research, I thought that didn’t involve tissue destruction, just genetics and developmental environment). I can feel the fight between the religious right and scientists in America brewing now.
Also from New Scientist: great news! New monkeys. Though from discovered to the endangered list in one day isn’t so good.

Whilst trawling the New Scientist site for content, I spotted this article, UN abandons legal ban on human cloning.

The declaration, which was passed by 84 votes to 34, with 37 abstentions, prohibits “all forms of human cloning inasmuch as they are incompatible with human dignity and the protection of human life”. But it has been widely criticised for being imprecise and meaningless.

I think imprecise and meaningless is a fair criticism; if you clone with dignity are you exempt from the interdiction? This little farce is caused by the split between people who want therapeutic cloning and those that think all cloning should be banned. The latter group often correlates with anti-abortionists (I prefer the name anti-abortion to pro-life as pro-life smacks of marketing bullshit; just say what you are), as while both therapeutic and reproductive cloning involves the creation of an embryo, therapeutic cloning involves the destruction of that embryo after stem cells have been harvested. No one in their right mind wants to proceed with human reproductive cloning (actually creating a genetic copy of a person); even ignoring any ethical reasons, the clone would have the same “genetic age” as the original person, as shown by Dolly the Sheep developing arthritis despite her young physical age. So the focus is on therapeutic cloning, which aims to generate a genetically identical embryo from which stem cells can be harvested and grown into replacement organs. (OK, whole replacement organs is actually quite a way outside our current abilities, but the report this week of a man being cured of type I diabetes by a cell transplant is an example of the use of this technique that could happen soon.) Stem cells are the progenitor cells from which many other cell types differentiate. Essentially they are uncommitted (I can identify with that) to any particular end cell type (be it skin, muscle, etc.). As an example of this kind of plasticity of function, think about potatoes; they are starch containing tubers and are specialised for this function, but leave them around on the kitchen worktop for a few days and they turn green and start photosynthesising. The cells change function. Admittedly this situation is different because the potato cells have differentiated into one type and are backing up and choosing a new path. Most human cells commit to one pathway early in development, hence the need for an embryo to get stem cells that can differentiate into any cell type. There was some talk of it being possible to harvest stem cells from amniotic fluid, but I don’t know if anything came of it. The argument for and against therapeutic cloning boils down to the “abortion” necessary to get these stem cells. Personally I’m not anti-abortion, so I don’t have any problem with the research; also, the potential cures for Parkinson’s, etc., weigh heavily in its favour. In addition, the clone embryo created is likely to suffer from the “genetic age” problem discussed above, and beyond that fact is unlikely to survive as 97% of cloning attempts fail. I think the general public would get behind stem cell research more if they realised just how cute the little blighters are.

Following my earlier post regarding evolution and intelligent design, I spotted a post on boingboing quoting a NYTimes article which fleshes out the argument for unintelligent design, citing extinction and some frankly comedic “design” in the plumbing of certain mammals. Vagaries in the route of the laryngeal nerve of the giraffe are perhaps a bit esoteric; the mere existence of the giraffe is good enough evidence for me. The extreme length of the giraffe’s neck means that its heart needs to be incredibly powerful in order to pump blood to the animal’s brain. Of course if the giraffe moves its head below the level of its heart, gravity is working in concert with this awesome pump, the unopposed combination of which would apparently generate enough force to blow the animal’s head clean off. (OK, maybe that’s hyperbole, but its a nice image.) To stop this, the giraffe has a valve to stop blood flowing up its neck when its head is in such a position. Still, it makes the “incredibly long neck” solution to finding food something I wouldn’t design, that valve smacks of post-production fixing after lots of headless prototype giraffes were found at watering holes. Actually this turns out to be one of the points creationists raise when they dis evolution.