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About this Author
DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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August 25, 2014

Citable Garbage

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Posted by Derek

Experimental and Clinical Cardiology used to be a reputable journal. Now it's a trash heap piled with crap. No, literally - the Ottawa Citizen newspaper has proof, thanks to reporter Tom Spears (who's an experienced hand at this). The journal was sold last year, and the new owners will publish absolutely anything you send them, as long as you send them $1200 to their bank account in the Turks and Caicos Islands. I wish I were making all that up, but that is exactly how it goes, offshore banking and all.

Spears whipped together a gibberish cardiology paper by taking one about HIV and doing a find-and-replace to substitute "cardiology" for "HIV" wherever it occurred. I'm sure it reads just fine, if you're high on crack. He stripped out all the graphics, wrote up some captions for new ones, but didn't send any graphs or figures with his submission. No problemo, dude! Paper accepted! As soon as the money shows up under that palm tree in the Caribbean, this junk will become the latest contribution to the medical literature.

The "journal" lists an affiliation with the International Academy of Cardiovascular Sciences in Winnipeg, which organization is pretty upset about that, since there's no connection at all any more. But how to get that fixed? The phone number listed for the editorial office doesn't work. And they don't respond to any emails that they don't feel like responding to, which I'd guess are all the ones that don't involve the possibility of $1200 wire transfers.

The wonderful people behind this scam will ride it as long as a shred of reputation clings to the journal's name, or as long as people send them money, whichever comes first. The journal's web site, which I will consider linking to if they pay me twelve hundred dollars, looks legit, except for the slightly-shaky-English-style notice that "Starting from Jan 1, 2013, Experimental and Clinical Cardiology Journal will operate under new publishing group". If you click "Editorial Board", it tells you that a new one is coming soon. And this part is pretty interesting, too - they say that they provide:

. . .outstanding service to authors through a clear and fast editorial process. Review and decision will be fast and our editorial policy is clear: we will either accept your manuscript for publication or not, our editors will not ask for additional research.

All submissions will be peer reviewed, and our reviewers are asked to focus their attention to data presented in the article. Your manuscript, after the review process can be or accepted or declined. Three independent reviewers are reviewing each manuscript and if two of them accept the manuscript then your work will be published without any further corrections. Note that we will not reject a manuscript because it is out of scope or for its perceived importance, novelty or ability to attract citations: we will publish any study that is scientifically sound.

Yeah boy! But as it says under "Publication Fees", "Open access publishing is not without its costs". One of those costs should be the scientific credibility of anyone who sends a paper in to the place these days. I've looked over the most recent papers listed on the web site - there's one from a hospital in Barcelona, a university in Turkey, an institute in China, some group from Italy whose paper doesn't load well, and a bunch of people with German-sounding names whose paper appears to be two pages long and consists of one figure and no text. An erratum? Who can tell? And who would bother? You might as well copy-and-paste some old Star Wars fan-fiction; no one's going to notice. Every single one of these lead authors probably had their paper turn around within a couple of days, and sent $1200 to the flipping Turks and Caicos without batting an eye, for a journal that's supposedly based in Switzerland. For shame.

No getting around it: if you send money to any of the publishers on Beall's List, you are funding a bunch of scam artists. And if you use such a paper to pad your own c.v., then you've decided to become a scam artist yourself.

Comments (7) + TrackBacks (0) | Category: The Dark Side | The Scientific Literature

July 7, 2014

That Retracted Stressed Stem Cell Work

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Posted by Derek

This article from David Cyranoski at Nature News is an excellent behind-the-scenes look at all the problems with the "STAP" stem-cell work, now retracted and apparently without any foundation at all. There were indeed problems with all of it from the start, and one of the key questions is whether these things could have been caught:

The committee was more vexed by instances of manipulated and duplicated images in the STAP papers. Obokata had spliced together gel lanes from different experiments to appear as one. And she had used an image of cells in a teratoma — a tumorous growth that includes multiple types of tissue — that had also appeared in her PhD dissertation. The captions indicated that the image was being used to represent different types of cell in each case. The committee judged that in both instances, although she might not have intended to mislead, she should have been “aware of the danger” and therefore found her guilty of misconduct. Obokata claimed that they were mistakes and has denied wrongdoing. . .

. . .Philip Campbell, editor-in-chief of Nature, says: “We have concluded that we and the referees could not have detected the problems that fatally undermined the papers.” But scientists and publishers say that catching even the less egregious mistakes raises alarm bells that, on further investigation, can lead to more serious problems being discovered.

Many say that the tests should be carried out on all papers. Christopher says that it takes about one-third of her working week to check all accepted manuscripts for the four journals published by EMBO Press. At Nature and the Nature research journals, papers are subjected to random spot-checking of images during the production process. Alice Henchley, a spokeswoman for Nature, says that the journal does not check the images in all papers because of limitations in resources, and that the STAP papers were not checked. But she adds that as one outcome of this episode, editors “have decided to increase the number of checks that we undertake on Nature’s papers. The exact number or proportion of papers that will be checked is still being decided.”

A complication is that some of the common image manipulations (splicing gel lanes, for example) are done in honest attempts to present the data more clearly, or just to save space in a figure. My guess is that admitting this up front, along with submitting copies of the original figures to the editors (and for inclusion in the Supplementary Material?) would help to clear that up. The article raises another good point - that editors are actually worried about confronting every example of image manipulation that they see, for fear of raising the competence of the average image manipulator. There's an evolutionary-arms-race aspect to all this that can't be ignored.

In the end, one gets the impression that Nature's editorial staff (a separate organization from the News people) very much regret ever having accepted the work, as well they might. Opinion seems divided about whether they could have caught the problems with the papers themselves - this was one of those cases where a number of reputable co-authors, at reputable institutions, all screwed up simultaneously when it came to cross-checking and verification. What remains is a portrait of how eager people can be to send in groundbreaking results for publication, and how eager editors can be to publish it. Neither of those are going to change any time soon, are they?

Update: from the comments, see also this timeline of events for a look at the whole story.

Comments (14) + TrackBacks (0) | Category: The Dark Side | The Scientific Literature

June 30, 2014

The GSK-China Situation Gets Even Weirder

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Posted by Derek

OK, the GlaxoSmithKline/China business has officially crossed over into new territory. Over the weekend, the company confirmed reports that Mark Reilly, the GSK executive in the country who's been in the middle of this affair from the beginning, was the object of a blackmail attempt by unknown parties. (The story was broken by the Sunday Times, and it's behind a paywall, but it's been picked up by every major news outlet).

Someone shot extensive footage of Reilly alone with his Chinese girlfriend, and mailed the resulting file to higher-ups at the company. The connection between all this and the corruption allegations has not been made clear, but the footage apparently accompanied some of the emails accusing the company of bribery. We may never know quite what's going on here, but I'll bet it's very interesting indeed. More on surveillance in China here.

Update: an excellent overview from the BBC.

Comments (36) + TrackBacks (0) | Category: Business and Markets | The Dark Side

June 27, 2014

Varieties of Scientific Deception

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Posted by Derek

Some may remember a paper from 2011 on the "reverse click" reaction, an interesting one where triazoles were pulled apart with mechanical force. This was an interesting system, because we really know surprisingly little, down on the molecular level, about what happens when bonds are physically stressed in this way. What do molecular orbitals look like when you grab both ends of the molecule and tug hard? Which bonds break first, and why? Do you get the reverse of the forward reaction, or do different mechanisms kick in (free radical intermediates, etc.)? (Note that the principle of microscopic reversibility doesn't necessarily apply when the conditions change like this).

Unfortunately, there seems to be trouble associated with this example. Science has an editorial "expression of concern" on the paper now, and it appears that much of it is not, in fact, reproducible (see this report in C&E News).

The paper was from the Bielawski lab at UT-Austin, and Bielawski is reported as saying that a former group member has confessed to manipulating data. But he also says that the conclusions of the paper are unchanged, which is interesting. My guess is that the "unclick" does happen, then, but nowhere as smoothly as reported. Someone may have sweetened things to make it all look better. At any rate, a correction is coming soon in Science, so we should get more information at that point.

This reminds me of the scheme I use to rate political and economic corruption. Stage I is paying someone off to do something they wouldn't normally do (or aren't authorized to do) for you. This happens everywhere, to some extent. Stage II is when you're bribing them just to do the job they're supposed to be doing in the first place. Many countries suffer from institutional cases of this, and it's supremely annoying, and a terrible drag on the economy. And Stage III, the worst, is when you're paying them not to harm you - a protection racket with the force of law behind it. Cynics may adduce examples from the US, but I'm thinking about countries (Russia, among others) where the problem is far worse.

Similar levels apply to fakery in the scientific literature. Here's how I break it down:

Stage I is what we may have in this case: actual conclusions and effects are made to look cleaner and better than reality. Zapping solvent peaks in the NMR is a perfect small-scale example of this - for organic chemists, solvent peaks are sometimes the training wheels of fakery. The problem is, once you're used to altering data, at what point do you find it convenient to stop? It's far better not to take that first step into matters-of-degree territory.

Stage II is unfortunately common as well, and there's a nice slippery path from Stage I that can land you here. This is when you're convinced that your results are correct, but you're having such a hard time getting things to work that you decide to "fake it until you make it". That's a stupendously bad idea, of course, because a lot of great results were never real in the first place, which leaves you hung out to dry, and even the ones that can be finally filled in don't have to do so in the way that you were faking them to happen. So now a real result is tainted by deception, which will call the whole thing into doubt when the inconsistencies become clear. And faked results are faked results, even if they're done in what you might think is a good cause. Many big cases of scientific fraud have started off this way, with someone just trying to fill in that one little gap, just for now.

Stage III, the bottom, is when something is faked from beginning to end. There was no question of it even working in the first place - it never did. Someone's just trying to get a paper, or a degree, or tenure, or fame, or something, and they're taking the shortcut. I think that there are two main classes of fakery in this category. In one group (IIIa?), you have people whipping up bogus results in low-profile cases where no one may notice for years, if ever, because no one cares. And you have IIIb, the famous high-profile cases (see Jan-Hendrik Schön, among too many others) where impressive, splashy, look-at-that stuff turns out to have been totally faked as well. Those cases are a study in human psychology. If you report a big result in superconductors, stem cells, cancer therapy or any other field where a lot of smart, competent people are paying very close attention, you will be found out at some point. How can you not be? We're in Bernie Madoff territory here, where someone comes into work every day of every week knowing that their whole reputation is a spray-painted scrim of deception that could have a hole punched through it any minute. How people can possibly live this way I don't really know, but people do. The self-confidence displayed by this sort of personality is a wonder of nature, in its way. IIIa cases are initiated by the desperate, stupid, and/or venal. IIIb cases, though, are brought on by people born to their task.

Update: as pointed out by several good comments, there are plenty of not-quite-fraud sins that neighbor these. Those are worth a separate post, partly because they're even more common than straight-up fraud.

Comments (53) + TrackBacks (0) | Category: The Dark Side | The Scientific Literature

June 2, 2014

No More Acid Stem Cells

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Posted by Derek

In case you hadn't seen it, the "acid-washed stem cells" business has gone as far into the dumper as it can possibly go. It now appears that the whole thing was a fraud, from start to finish - if that's not the case, I'll be quite surprised, anyway. The most senior author of the (now retracted) second paper, Teruhiko Wakayama, has said that he doesn't believe its results:

The trigger, he told Bioscience, was his discovery—which he reported to Riken a few weeks ago--that two key photos in the second paper were wrong. Obokata, lead author on both papers, had in April been found by Riken guilty of misconduct on the first paper: the falsification of a gel electrophoresis image proving her starting cells were mature cells, and the fabrication of images proving resulting STAP stem cells could form the three major tissue types of the body.

But Riken had not yet announced serious problems with the second paper.

Last week, however, there was a flurry of activity in the Japanese press, as papers reported that two photos—supposed to show placenta made from STAP cells, next to placenta made from embryonic stem (ES) cells—were actually photos of the same mouse placenta.

As with so many cases before this one, we now move on (as one of Doris Lessing's characters once put it) to having interesting thoughts about the psychology of lying. How and why someone does this sort of thing is, I'm relieved to say, apparently beyond me. The only way I can remotely see it is if these results were something that a person thought were really correct, but just needed a bit more work, which would be filled in in time to salvage everything. But how many times have people thought that? And how does it always seem to work out? I'm back to being baffled. The stem cell field has attracted its share of mentally unstable people, and more.

Comments (12) + TrackBacks (0) | Category: Biological News | The Dark Side | The Scientific Literature

May 14, 2014

China Raises the Stakes in the GSK Scandal

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Posted by Derek

GSK's troubles in China have just gotten even more serious. The government has formally charged Mark Reilly, former head of the company's operations in China, of organizing and participating in a bribery scheme. This seems to have been a stronger step than people were expecting - we'll see what happens. Reilly's whereabouts do not seem to be clear to anyone - I would assume that he left China some time ago, but if he hasn't, then he's not leaving for some time to come.

Comments (11) + TrackBacks (0) | Category: Business and Markets | The Dark Side

April 22, 2014

J. Appl. Drivel or Gibberish Lett.? Choices, Choices.

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Posted by Derek

People keep hoaxing the predatory "scholarly" publishers out there, and the publishers keep falling for whatever drivel is slung at them. Here's the latest example from a reporter at the Ottawa Citizen, Tom Spears. He molded a pile of steaming gibberish into the rough shape of a manuscript, and that was more than enough:

I have just written the world’s worst science research paper: More than incompetent, it’s a mess of plagiarism and meaningless garble. . .

. . .I copied and pasted one phrase [in the title] from a geology paper online, and the rest from a medical one, on hematology.

I wrote the whole paper that way, copying and pasting from soil, then blood, then soil again, and so on. There are a couple of graphs from a paper about Mars. They had squiggly lines and looked cool, so I threw them in.

Footnotes came largely from a paper on wine chemistry. The finished product is completely meaningless.

The university where I claim to work doesn’t exist. Nor do the Nepean Desert or my co-author. Software that catches plagiarism identified 67 per cent of my paper as stolen (and that’s missing some). And geology and blood work don’t mix, even with my invention of seismic platelets.

And you guessed it - the acceptances came rolling in, and pretty damned quickly, too. Peer-reviewed, refereed, and edited within 24 hours - where are you going to find an honest journal with service like that? 16 of the 18 bottom-feeding "journals" accepted it, and one of the rejections suggested that it just needed a bit of tweaking to be accepted. And one of the publishers has asked Spears to serve on an editorial advisory board, so he's clearly got what it takes.

Of course, as yesterday's post shows, even a peer-reviewed journal with a recognizable name can publish gibberish. But I assume that Drug Discovery Today and Elsevier didn't charge the author $1000 to do it. On the other hand, they might have taken more than 18 hours to review the manuscript. Or not.

Comments (14) + TrackBacks (0) | Category: The Dark Side | The Scientific Literature

April 16, 2014

Professor Fukuyama's Solvent Peaks

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Posted by Derek

See Arr Oh expresses some doubts about all the NMR spectral corrections we've been seeing lately. He's specifically referring to Bethany Halford's interview piece, and he has this to say after reading it:

If your group focuses on "clean up your spectra" more than "purify your compounds better," that's a communications issue. If a professor with a large group sees nothing but perfect spectra all day, two thoughts should crop up:

1. "I must have the smartest, most efficient students in the world," or...
2. "Something's fishy here."

Perfect-looking data should always be a cause for concern in any experiment. My guess is that Prof. Fukuyama was closer to Option One, though, possibly in the variant of "My group has such high standards!" But high standards or not, a series of perfect, flat, NMR spectra with no solvent and no impurities is rather hard to achieve in total synthesis, considering the quantities that are being used. Load up the tube with 50mg of material and you can make a lot of stuff look good, but you don't have fifty mgs at step thirty-four, do you? I remember putting everything I had into one NMR tube (or worse, one polarimeter tube) in my own total synthesis days, and I carried the thing down to the machine like it was a bag of gold.

But there's no doubt that in a big group, there will be people who try to slip things past the boss. I've seen it myself; I'm sure that a lot of you have. And if you're giving the boss exactly what the boss wants to see - perfection - then it's going to be a lot easier. These spectral problems look like a collaborative effort to me - expectations from above, willingness from below. And there are a lot of other groups that have done (and, I feel sure, still do) the same thing. Zapping the solvent peaks in the NMR is the least of it, in some cases.

Update: added a direct link to the Fukuyama/Yokoshima interview.

Comments (19) + TrackBacks (0) | Category: The Dark Side | The Scientific Literature

March 28, 2014

More on the UT-Austin Retraction Case

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Posted by Derek

I mentioned an unusual retraction from Organic Letters here last year, and here's some follow-up to the story:

Nearly six years after Suvi Orr received a Ph.D. in chemistry from the University of Texas, the university told her it has decided to do something that institutions of higher learning almost never do: revoke
the degree. Orr, in turn, has sued UT in an effort to hold onto the doctorate that launched her career in the pharmaceutical industry.

Her lawsuit in state district court in Travis County contends that revocation is unwarranted and that the university violated her rights by not letting her defend herself before the dissertation committee that condemned her research long after she graduated. In addition, she says, the committee relied heavily on her former professor, who, she claims, was motivated to “cast the blame elsewhere.”

What a mess. More details as things develop. . .

Comments (17) + TrackBacks (0) | Category: The Dark Side | The Scientific Literature

February 26, 2014

The Instructive Case of Galena Biopharma

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Posted by Derek

If you're in the mood for another reason why you should always be cautious about your biopharma investments, look no further than Galena Biopharma (GALE to its many clueless fans). I've been following this story over the last couple of weeks, and what a mess it is. Galena is a small company in Oregon with a few assets, including a cancer vaccine candidate. Its stock hovers in the low single digits, as is appropriate. But in December and January, it began to trade up, and up. From $2/share to $4. Then to $6, and then higher. And this on no particular news or change in the company's prospects, which for a stock like this is often a sign of "momentum" players getting involved. "Momentum" investing is a fancy name for "I'm buying this because it's going up", and the people who do this sort of thing are understandably anxious for you to buy some, too. They're also very, very unwilling to hear about anything that might cause the stock to go back down, because the proper direction for stocks, we must remember, is up. They only go down because of evil short bashers; everyone knows this.

Adam Feuerstein of TheStreet.com delivered a great big dose of that evil stuff (known to the rest of us as "reality") on February 12 with this article, which showed why the stock had been rising. The company was paying a PR firm to beat the drums for it, said drum-beating going as far as having people post multiple supposedly-independent articles on sites like Seeking Alpha under a list of pseudonyms.

An outfit called the "DreamTeam Group" was hired for the promotion. They run a stable of stock-touting web sites, full of wonderful tales about the companies that are paying them to say these wonderful things. And they spread the word on other sites (as above), and on Twitter, by e-mail and whatever means come to hand. If carrier pigeons come back into fashion, you can count on one fluttering down with a hot stock tip for you. And if you're greedy and stupid, you could see all this hype and convince yourself that a Great Opportunity is spawning right in front of you - why, all these people are buzzing about this hot little company, and money is right there for the taking. The only reason not to get in on a deal like this would be a lack of vision.

Galena's insiders do not lack vision. Indeed, they have proven beyond any doubt that money was in fact there for the taking. GALE peaked at nearly $8/share, but its directors and officers were unloading millions of dollars worth of shares into that market. And who could blame them? These are legal financial transactions between consenting adults, and if one set of those adults know what's going on and the other set doesn't, well, it's that kind of world, isn't it? A look at any jungle will show the larger predators eating the smaller ones, and God knows the Street isn't any different.

Yesterday GALE closed at about $4, and many of its "investors" are hopping mad about that, as a look at Feuerstein's mailbag will show. But here are some cynical people who figure that the company is actually worth about seventy-two cents a share. Reasonable observers can disagree about that figure. But if you want to argue that the company is cruelly undervalued at $4, you are probably not a reasonable observer. Or you bought at $7. Same thing.

Update: if you'd like to know why people are so skeptical of the prospects for Galena's vaccine, look no further than this comment. It's right on target.

Comments (64) + TrackBacks (0) | Category: Business and Markets | The Dark Side

February 14, 2014

"It Is Not Hard to Peddle Incoherent Math to Biologists"

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Posted by Derek

Here's a nasty fight going on in molecular biology/bioinformatics. Lior Pachter of Berkeley describes some severe objections he has to published work from the lab of Manolis Kellis at MIT. (His two previous posts on these issues are here and here). I'm going to use a phrase that Pachter hears too often and say that I don't have the math to address those two earlier posts. But the latest one wraps things up in a form that everyone can understand. After describing what does look like a severe error in one of the Manolis group's conference presentations, which Pachter included in a review of the work, he says that:

. . .(they) spun the bad news they had received as “resulting from combinatorial connectivity patterns prevalent in larger network structures.” They then added that “…this combinatorial clustering effect brings into question the current definition of network motif” and proposed that “additional statistics…might well be suited to identify larger meaningful networks.” This is a lot like someone claiming to discover a bacteria whose DNA is arsenic-based and upon being told by others that the “discovery” is incorrect – in fact, that very bacteria seeks out phosphorous – responding that this is “really helpful” and