My friend Björn has just been published in the Proceedings of the Royal Society, an invited article on the possible biological basis of free will.

In accordance with Björn's commitment to openness in science, he circulated a preprint and paid to make the published version Open Access in the hope of stimulating further discussion:

The article has been through several rounds of peer-review, both informal and formal [...] since august this year. Of course, the real discussion, I would hope, isn't starting until today, when the article actually became accessible.

I read the preprint, and it made my head ache. In a good way. I'm really not qualified to say whether Björn is right or wrong or completely nuts on this issue, but he's taken an ambitious stab at a Big Question and that's always good. More to the point, he's done it well and carefully and it's worth your time to play along at home.

Do your brain a favor and give it a workout -- the full article is freely available online, and if you have substantive comments to make I guarantee you that the author will be delighted.

To whet your appetite, here's the abstract:

Until the advent of modern neuroscience, free will used to be a theological and a metaphysical concept, debated with little reference to brain function. Today, with ever increasing understanding of neurons, circuits and cognition, this concept has become outdated and any metaphysical account of free will is rightfully rejected. The consequence is not, however, that we become mindless automata responding predictably to external stimuli. On the contrary, accumulating evidence also from brains much smaller than ours points towards a general organization of brain function that incorporates flexible decision-making on the basis of complex computations negotiating internal and external processing. The adaptive value of such an organization consists of being unpredictable for competitors, prey or predators, as well as being able to explore the hidden resource deterministic automats would never find. At the same time, this organization allows all animals to respond efficiently with tried-and-tested behaviours to predictable and reliable stimuli. As has been the case so many times in the history of neuroscience, invertebrate model systems are spearheading these research efforts. This comparatively recent evidence indicates that one common ability of most if not all brains is to choose among different behavioural options even in the absence of differences in the environment and perform genuinely novel acts. Therefore, it seems a reasonable effort for any neurobiologist to join and support a rather illustrious list of scholars who are trying to wrestle the term 'free will' from its metaphysical ancestry. The goal is to arrive at a scientific concept of free will, starting from these recently discovered processes with a strong emphasis on the neurobiological mechanisms underlying them.

Unless you've been living under a rock, you'll be aware of the latest round of anti-vaccine inanity, but unless you've taken some time to look into it you might not be aware of quite how stupid, and how dangerous, the anti-vaccine "crusade" really is.

In either case, do yourself and everyone else a favor and go read Shirley's open letter to Oprah.

@Oprah, don't watch show but nice Duke speech. take own advice and make difficult decision to pull support from mccarthy, save lives. kthxbi

It's a quick read, but contains all the facts you'd want at your fingertips and pointers to plenty more. It's also warm and calm and human, and strikes me as being far more likely to actually get Oprah to reconsider her stance than some of the angrier and/or more science-focused commentary out there.

So go read it, blog about it, retweet it. See if we can get Oprah's attention.

I don't normally promote new blogs, other than to add them to my blogroll if I think they are worth my readers' time, but I'll make an exception for PLoS ONE's new community blog, EveryONE:

Why a blog and why now? As of March 2009,  PLoS ONE, the peer-reviewed open-access journal for all scientific and medical research, has published over 5,000 articles, representing the work of over 30,000 authors and co-authors, and receives over 160,000 unique visitors per month. That's a good sized online community and we thought it was about time that you had a blog to call your own. This blog is for authors who have published with us and for users who haven't and it contains something for everyone.

Why did you call the blog everyONE? For three main reasons that encapsulate the mission of the journal:

Firstly, because PLoS ONE is for every rigorous research article that passes our peer-review process.

Secondly, because PLoS ONE is a forum for research in every scientific discipline (with a current emphasis on life and health sciences because of PLoS's history).

Thirdly, because PLoS ONE is a source of information for every inquisitive reader with an interest in high-quality scientific research.

I hope, and on my better days believe, that PLoS ONE is one of the leading models for the future of scientific journals:

• they offer gold OA -- that is, free online to everyone everywhere from the moment of publication, including submission to PubMed Central
• they offer a sustainable business model for OA: in the black after less than three years and with an author-side fee of $1300
• their peer review process is as rigorous as any, but it does not ask reviewers to make guesses about what is "hot", or what is likely to be important at some time in the future: if it's solid science, PLoS ONE will publish it
• they don't have an Impact Factor: homey don't play dat, as the kids around here say
• that's not to say that they are not actively seeking rich measures of utility/impact for scientific publications: for instance, here's Bora's roundup of analyses of an experimental dataset that they passed around a while back, and an update from Euan
• in the same vein, I can't find a link right now but there are plans afoot to release real-time access to such data as downloads, comment frequency and so on -- post-publication measures which can improve and speed up citation based measures; for another example, scroll down on this page for some self-measurement that represents a level of disclosure I have not seen from any other journal
• they are responsive to and engaged with the community: for instance, both Bora Zivkovic (community manager -- how many journals have one of those?) and Peter Binfield (managing editor) are active on FriendFeed
• they encourage and enable community input in the form of notes, comments and ratings on every article; I particularly like the option given to reviewers to have their reviews included as comments with the paper

EveryONE is another way for PLoS ONE to engage with their community of readers and contributors, and well worth a look.

DISCLAIMER: I consider Bora and Peter friends of mine, and I've previously applied to work at PLoS.

Mike of Bioinformatics Zen is looking for information; please help him out if you can, by taking the survey either here or at BZ. Take particular note of the following:

The raw data entered into this questionnaire, along with any interpretation will be released into the public domain under a creative commons attribution license. If you are unhappy with answering any of the questions please leave them blank. By completing this questionnaire you consent to your answers being released.

(Yes, I know it's repeated at the top of the survey: it's important.)

I'm always a bit leery of edge.org, seeing as how it's first and foremost a promotional vehicle for John Brockman's stable of authors, but I do enjoy the Annual Question. This year's is no exception:

When thinking changes your mind, that's philosophy.
When God changes your mind, that's faith.
When facts change your mind, that's science.

WHAT HAVE YOU CHANGED YOUR MIND ABOUT? WHY?

Science is based on evidence. What happens when the data change? How have scientific findings or arguments changed your mind?"

What struck me about the answers was that a number of them point out, if indirectly, that the wording of the question is utter bollocks. Whoever wrote the question has drunk deep of the "impartial search for Truth" Kool-Aid and needs an infusion of Kuhn¹ (or a week in an actual lab), stat.

Roger Highfield comes right out and says it:

I am a heretic. I have come to question the key assumption behind this survey: "When facts change your mind, that's science." This idea that science is an objective fact-driven pursuit is laudable, seductive and - alas - a mirage.

Science is a never-ending dialogue between theorists and experimenters. But people are central to that dialogue. And people ignore facts. They distort them or select the ones that suit their cause, depending on how they interpret their meaning. Or they don't ask the right questions to obtain the relevant facts.

That science is nothing like the simplistic picture we were all fed in school seems to be something of a theme in the answers to this year's Edge question:

Colin Tudge:

I have changed my mind about the omniscience and omnipotence of science. I now realize that science is strictly limited, and that it is extremely dangerous not to appreciate this.

Francesco de Pretis:

In two weeks I finished the book [that changed my mind] and then my way of thinking changed. I understood that science was not only a pursuit of knowledge but a social process too, with its rules and tricks: a never-ending tale such as human life.

Irene Pepperberg:

I've begun to rethink the way we teach students to engage in scientific research. I was trained, as a chemist, to use the classic scientific method: Devise a testable hypothesis, and then design an experiment to see if the hypothesis is correct or not. And I was told that this method is equally valid for the social sciences. I've changed my mind that this is the best way to do science. I have three reasons for this change of mind.

First, and probably most importantly, I've learned that one often needs simply to sit and observe and learn about one's subject before even attempting to devise a testable hypothesis. [...]

Second, I've learned that truly interesting questions really often can't be reduced to a simple testable hypothesis, at least not without being somewhat absurd. [...]

Third, I've learned that the scientific community's emphasis on hypothesis-based research leads too many scientists to devise experiments to prove, rather than test, their hypotheses.

Robert Provine:

Mentors, paper referees and grant reviewers have warned me on occasion about scientific "fishing expeditions," the conduct of empirical research that does not test a specific hypothesis or is not guided by theory. Such "blind empiricism" was said to be unscientific, to waste time and produce useless data. Although I have never been completely convinced of the hazards of fishing, I now reject them outright, with a few reservations.

I'm not advocating the collection of random facts, but the use of broad-based descriptive studies to learn what to study and how to study it. Those who fish learn where the fish are, their species, number and habits. Without the guidance of preliminary descriptive studies, hypothesis testing can be inefficient and misguided. Hypothesis testing is a powerful means of rejecting error -- of trimming the dead limbs from the scientific tree -- but it does not generate hypotheses or signify which are worthy of test.

Robert Shapiro:

I used to view the scientific literature as a collective human effort to build an enduring and expanding structure of knowledge. Each new publication in a respected, refereed journal would be digested and debated... [b]ut once it has passed scrutiny, a new contribution would be absorbed into the edifice of science, expanding and enhancing it, while providing a fragment of immortality to the authors.

My perception was wrong. New scientific ideas can be smothered with silence.

Steve Nadis:

At its heart, science is a human endeavor, carried out by people. When the questions are truly ambitious, it takes a great personal commitment to make any headway -- a big investment in energy and in emotion as well. I know from having met with many of the lead researchers that the debates can get heated, sometimes uncomfortably so. More importantly, when you're engaged in an epic struggle like this -- trying, for instance, to put together a theory of broad sweep -- it may be difficult, if not impossible, to keep an "open mind" because you may be well beyond that stage, having long since cast your lot with a particular line of reasoning. And after making an investment over the course of many years, it's natural to want to protect it.

A. Garrett Lisi:

...the ambivalence associated with an even probability distribution makes it terribly difficult for an ideal scientist to decide where to go for dinner. [...]

Ken Ford:

I used to believe that the ethos of science, the very nature of science, guaranteed the ethical behavior of its practitioners. As a student and a young researcher, I could not conceive of cheating, claiming credit for the work of others, or fabricating data. Among my mentors and my colleagues, I saw no evidence that anyone else believed otherwise. And I didn't know enough of the history of my own subject to be aware of ethical lapses by earlier scientists. There was, I sensed, a wonderful purity to science. Looking back, I have to count naiveté as among my virtues as a scientist.

Now I have changed my mind, and I have changed it because of evidence, which is what we scientists are supposed to do. Various examples of cheating, some of them quite serious, have come to light in the last few decades, and misbehaviors in earlier times have been reported as well. Scientists are, as the saying goes, "only human," which, in my opinion, is neither an excuse nor an adequate explanation.

Rebecca Goldstein:

Popper's characterization of how science is practiced --as a cycle of conjecture and refutation -- bears little relation to what goes on in the labs and journals.

______
¹ Yes, I read SSR fairly recently, and it gave me a clear structure for a lot of vague suspicions I'd been entertaining since grad school. I suspect I'm doing that "ooh, philosophy of science, yeah, I read Kuhn" thing that probably drives real philosophers of science bugfuck. By way of mitigation, the latter are invited to recommend further reading.

Well, one answer is that they are MEFs -- mouse embryo fibroblasts -- since that's what I started with. Only the cells pictured are pretty clearly not regular fibroblasts; they look more like neurons or macrophages of some kind. MEFs are a mixed population, consisting of whatever grows out of a dissociated (minced) mouse embryo minus the head, so there are some early neural and immune cells in the mix. The cells pictured are what remains after selection with either G418 or puromycin -- I was making stably transfected cells, and this is one of the control plates.

So what I'm wondering is, would a brief period of exposure to a selective agent like puro be a good way to isolate naturally resistant populations, and what would those populations contain? (Of course, whatever these things are, the most likely explanation for their resistance is terminal differentiation, so they're simply dying more slowly -- I haven't tried taking away the selective agent to see whether they will multiply.)

Any ideas, lazyweb?

Nature recently published an editorial in which they discussed an update to their 1869 (!) mission statement. The editorial is subscription-only, but Maxine published an excerpt on Nautilus, which I further excerpt here:

The original mission statement of this journal, first printed in Nature's second issue on 11 November 1869, was... running behind the times when it referred to "Scientific men" ... In other respects it is well worded -- which is why we print it every week in the Table of Contents.
[...]
In printing the statement verbatim every week as we have done, making it clear when it originated, we have hitherto assumed that readers will excuse the wording in the interests of historical integrity. But feedback from readers of both sexes indicates that the phrase, even when cited as a product of its time, causes displeasure. Such signals have been occasional but persistent, and a response is required.
There is a convention within the English language by which writers quoting text can indicate their view that a particular phrase is inappropriate. That is to insert sic, a Latin word meaning 'thus', after the phrase -- in effect expressing the sentiment 'alas, dear reader, this is what was said'.
This is what we will do in the mission statement from now on. The small, belated change takes place against the vast backdrop of a scientific world where the upper echelons of academia, academies and prestigious awards are still numerically greatly dominated by men, and where outright discrimination can still rear its ugly head... In this context, the insertion of a Latin word in a couple of paragraphs may be a tiny step: but it is at least one in the right direction.

Zuska took offence, and I was a bit puzzled myself so I went and asked Maxine to clarify:

This decision puzzles me. Why not simply change the wording (s/'Scientific men'/scientists) and say "we've updated the statement to better reflect our modern aims"?

Mission statements that date to 1869 are pretty damn cool, I'll grant you -- but it seems that here tradition is trumping concerns (which NPG obviously shares!) about inclusive language. Why take a "tiny step... in the right direction" when the whole step is so easy to take instead?

Maxine's response:

We did update our mission statement years ago, and I've added a link to the newer version (on the "about the journal" page in my post above, in light of your comment.
What the Editorial said was that the "original" mission statement would contain this correction, on any future occasions where we reprint it. It did not mean to imply that we had not updated our mission statement since 1869.

So that makes more sense; but as Zuska points out, there is some confusion over which statement is going to appear where. So, being a scientist -- we learn by doing -- I went and looked.

Online: I started by typing in www.nature.com and looked around the page for some kind of "about Nature" resource. The first thing I found was About NPG under "Information" at the bottom of the page -- since I was actually at the Nature Publishing Group homepage, Nature the journal being actually at www.nature.com/nature.

On the About NPG page, under "Browse", "Company Information", there's a link to mission, whereat we find the original in all its sexist glory.

From www.nature.com/nature (the journal itself), the obvious place to look is the About the journal link, which goes to the modern mission statement and includes a clearly labeled link to the same 1869 version as "mission" above.

In meatspace: I went to our little library here at work and picked up a physical copy of Nature for the first time in probably ten years. (Full disclosure, or something: it was the chimp genome issue, vol 437 issue 7055, Sept 2005.) The first five pages are full-page ads, and then comes the table of contents. In a sidebar on the left hand side is the following quote from the original mission statemtent, under the heading "NATURE'S MISSION, 1869:"; I've used a scan of the sidebar as a sort of sidebar for this entry. Note that this is not quite the same as, but not substantively different from, the online version.

So now at least I know what it is that I disagree with. I don't think NPG should link to the 1869 statement, at least not without going through the modern version, as Nature (the journal site) does. I think the print journal should print the modern mission statement -- with, if they want a nod to their impressive history, a comment to the effect that apart from updating sexist and exclusive language, not much has changed from the original (which is visible on our website, etc etc).

Andrew Hessel in MungBeing Magazine, quoted (approvingly, to my astonishment) by Jonathan Eisen:

Twenty five years ago, kids flocked to computers, pushing the limits of what they could do. Similarly, the next generation of genetic engineers won't need laboratories or even PhD: they'll have laptops, cheap mail order DNA synthesis, and, thanks to Google and Wikipedia and open journals like PLOS Biology, access to mountains of free biological data. They'll work in basements, garages, and cafes, and they'll trade ideas and collaborate on genetic designs the same way open source programmers now write computer code. Keep in mind that it was only 30 years ago that a little company called Apple started out of a California garage.

Which reminds me of Freeman Dyson in the NYRB a while back:

Every orchid or rose or lizard or snake is the work of a dedicated and skilled breeder. There are thousands of people, amateurs and professionals, who devote their lives to this business. Now imagine what will happen when the tools of genetic engineering become accessible to these people. There will be do-it-yourself kits for gardeners who will use genetic engineering to breed new varieties of roses and orchids. Also kits for lovers of pigeons and parrots and lizards and snakes to breed new varieties of pets. Breeders of dogs and cats will have their kits too.

Most of that is, in my opinion, complete and utter bollocks.

Despite the attractive and often useful analogy, genomes are not really software, and bio-tinkering is nothing like coding. It takes a lot more time and equipment, for one thing. There's a reason you don't see many people building jet airplanes for fun. When is "cheap DNA synthesis" going to be available to the general public? Who is going to sell J. Random Teenager a PCR machine? Don't wave your hands and airily declaim that everything is possible and it's someone else's job to make it work (as Dyson did while he was flogging his book in the NYRB): describe for me the business model. Sure, in theory you can do those experiments in your kitchen -- but have you ever actually tried it? Take it from someone who does them for a living, you don't have the patience to make it work. No one does. It's one thing to hack away at a piece of code until it runs the way you want; it's quite another to "hack" something in which every change requires several weeks' worth of complex and time-consuming manipulations, to say nothing of a generation or ten.

And then there's regulatory oversight. We let people hack away at computers as much as they can stand, but a computer is not a living thing. It's not cruelty if you get mad at your linux box and pound it into flinders. Those pigeons and lizards and parrots and cats are not toys; they can suffer, and if you let Joe Public futz with their genomes they will -- horribly. (I happen to think a good percentage of pet breeders are scum, too. What kind of despicable arrogance is required to manipulate a living genome for nothing more than your own twisted aesthetic pleasure? You people with the dogs and cats whose faces are so squished they can barely breathe -- you're sick.)

Further to the question of oversight, let's think about consequences. You've seen computer viruses: think about a world in which Kevin Mitnick meets Dylan Klebold at a smallpox swap-meet. How do you like your brave new world of garage biology now? And that's just the potential for malicious success -- the dangers of stupidity and failure loom considerably greater. Get your syntax wrong or wire your motherboard the wrong way around and, well, nothing much happens. Fuck up a genome, though, and see how you like the result -- especially if it survives.

The Hessel/Dyson version of our biotech future is not going come into being. Not in a decade, not in a millennium, not ever. Quite apart from its being about as likely in practical terms as me learning to fly by flapping my arms, we -- as a society -- will not let it happen. Not if we have any bloody sense at all.

Dr Shellie has run the job search gauntlet and -- O frabjous day! Callooh! Callay! --- has multiple appealing offers from which to choose.  Reflecting on the process, and her years of anxiety leading to this point, she says:

... I think that if your goal is to get a tenure-track job at a research university in a place you want to live, it's hard to know your chance of success much in advance. Many smart people with excellent records do not get jobs. Which is too bad, since it can take 5-10 years just to get ready to apply -- counting the time you spend in a PhD and a postdoc. And how are you supposed to predict your chances then -- when you are starting grad school?

How indeed? I don't think the situation for postdocs has improved since this article appeared in 2002. In biomed research, I would guesstimate that about 10% of postdocs end up with "their own lab". Worse, this is not simply tough competition -- so many personal/political factors enter into the success equation that you might as well roll dice as try to forecast your future as a researcher by any rational method. It's my blog, so I'll go ahead and quote myself:

The system is broken: there are too many PhD graduates and not enough real jobs for them. A postdoc is not a real job; even a tenure-track position, one step up the foodchain from a postdoc, is not a real job. A real job will not be yanked out from under you every few years, unless you or your boss can continually win funding -- and when you get down to 20% funding levels, between politics and the sheer volume of work dumped on the granting committees, you might as well pick the names out of a hat. A real job does not leave you entirely at the mercy of your superiors, who can demand insane work hours from you, knowing that if you won't sacrifice your life on the altar of their lab/department/whatever, there are ten other PhDs clamoring for the chance to do so. I'm no fan of the dismal science, but the law of supply and demand does seem to be consistent with observed phenomena here.

Now, that gloomy beginning notwithstanding, this is not another postdoc complaint post. (That one is in the works; I'm saving up links for it here and here.) Right now I want to take a much more positive perspective, inspired by Dr Shellie, who asks:

How should I think about recruiting graduate students, when I am encouraging them to pursue an uncertain career path?

This is a very good question indeed, and the best thing about it is that a newly-minted research professor is asking it! Is it really ethical (anyone? anyone? BuellerFree-Ride?) to encourage students into grad school, given that the standard "career path" is long, tortuous and more than likely to land the weary traveler somewhere other than that fabled destination, the faculty slot?

Another way of looking at this is to ask: is the system so irreparably broken that we should dismantle it -- starting by turning away grad students -- or can we work with what we have, and fix it?  I'm a meliorist rather than a revolutionary myself.  Further, if you want to be a PI yourself you're going to have to take on grad students, and more generally if we want research to flourish we, as a community, are going to need grad students. 

So, since we're going to continue to lure bright-eyed, unsuspecting college kids into the postdoc trap via grad school, what can we do to reduce harm?  Herewith some thoughts:

1. Inform, inform, inform.  Let 'em know upfront what they're getting themselves into. 

1b. Repeat, repeat, repeat.  They're young, they'll think "it won't happen to me".  We're all bulletproof at eighteen.

2. Present alternatives, and treat those alternatives with respect.  Don't be another type-A asshole in a labcoat who thinks, and acts as though, any deviation from the One True And Shining Path To Glory (why, research of course) represents complete failure as a scientist and as a human being.  Scientists reading this are nodding their heads, the rest of you are probably thinking huh? surely he exaggerates -- but I assure you I don't.  Throughout the community of science, at least in academia where I've spent most of my time, there is a powerful and pervasive assumption that research is the pinnacle of human endeavour and that a person would only do something else because they couldn't make the grade in research.   This is not a conscious belief, it's a largely unexamined background of feeling, something absorbed by intellectual and emotional osmosis from a peer group of self-involved, highly-focused people who have, given their material situation, a deep investment in believing they are doing something that sets them apart and above.  It is also, of course, utter and unmitigated horseshit.  Don't perpetuate it.

3. Give a damn.  Your students are not fungible data-production units, they're people with lives outside the lab, hopes, dreams, and all that crap.  You don't have to get all touchy-feely if that's not your style -- just understand that some of your students will find that they don't want your job after all -- and that's OK.  Some will even start out with other destinations in mind -- and that's a good thing.  Wouldn't you like to see more people with solid research experience go into teaching, journalism, policy development, marketing, law, medicine and a dozen other vital professions?  Wouldn't you like to see an ecologist become US President right about now?  Don't take it as a personal affront if someone doesn't make emulating you their sole ambition; take the time to consider what might be best for them.

I'm sure there's more -- comments, please!  For one thing, I am clinging still to the last forlorn threads of hope that I might be taking on students myself one day, and those putative students will need all the help I can get.

Finally, to Dr Shellie, an answer of sorts: if you're asking yourself at this early stage whether it's ethical even to take on students, then you are probably just the sort of PI who should be taking on students, and who will provide them with solid lab experience with which they can do whatever they want -- even research.

I hate antibodies. There, I said it. When they work, they are an exquisite tool; when they don't, which seems to be most of the bloody time, they are an infuriating waste of money and effort.

About the only thing I hate more than antibodies is shopping, especially comparison shopping, for antibodies. Biocompare is OK, but not great -- and I distrust all commercial comparison-shopping services anyway, since I figure they sell priority listings.

Enter the internets: Alf recently pointed to a dynamic version of Google's custom search, and Nature recently published a tech feature on antibodies -- including a nice long table of suppliers, complete with websites.

So for now, here's the crude version: I just jammed both those things together onto a single page: Google Custom Antibody Search.

What I'd like to do, eventually, is to turn the thing into a communal resource. This will mean finding a way to make it quick and easy for anyone to add a new suppliers' website. I could put it on a wiki somewhere, but I'd like to be able to offer a one-click way for people to contribute... maybe a one-click Simpy button with a tag like "AbSupplier", a way to produce a non-redundant subset of the links so tagged, and then a way to write those links back out to the custom search page...

Anyway, there it is. I don't even know for sure that it will be useful -- I'll try it myself at work, and see. Feel free to leave a comment here suggesting ways I could improve it, or just take the idea and build the thing properly yourself.


... wait, that's not a mashup, is it? If I got it working with Simpy or something, then it'd be a mashup. Poo.

Via Peer-to-Peer, Ariberto Fassati in this week's Nature correspondence (sorry, toll access only):

Reviewers [of scientific publications] often make significant contributions in shaping discoveries. They suggest new experiments, propose novel interpretations and reject some papers outright. [...] It is well worth keeping a record of such work, for no history of science will be complete and accurate without it.

I therefore propose that journals' records should be made publicly available after an adequate lapse of time, including the names of reviewers and the confidential comments exchanged between editors and reviewers. The Nobel Foundation makes all its records available after 50 years, as do many governmental and other institutions. This delay may be reduced for scientific journals to, perhaps, 15 or 20 years.

Now that's a damn good idea: it's long past time that reviewing got its due as an essential part of a scientist's job, and opening the records should help to generate such recognition (to say nothing of the invaluable contribution to historiography of science).

My only quibble: why 15 years? If six months is long enough for an embargo on a closed-access paper, why is it not also long enough to keep the reviews secret? I presume the idea is to prevent retaliation for harsh reviews, but if all the information is public it would take a truly dedicated holder of a truly heinous grudge to follow up (in such a way as not to get caught doing it!) after six or twelve months. More to the point, we can dramatically reduce the risk of such retaliation by changing the community attitude towards reviewing. If peer review becomes a fully acknowledged part of the job, excellence in which is respected and rewarded -- and if everyone knows their reviews will be made public! -- then low quality (gratuitously mean, ill-informed, lazy, self-serving, etc) reviews should be a thing of the past.

Janet Stemwedel is a bit bummed out by all the cynicism in her comments section lately:

What's sticking in my craw a little is the "Eh, what are you gonna do?" note of resignation about some of the problematic behaviors and outcomes that are acknowledged to be even more common than the headlines would lead us to believe.

Janet claims that "Norms are what we ought to do, not what we suspect everyone actually does". Me, I think "norms" is used to describe both sets of behaviours, and when observed behaviour norms differ from espoused value norms, there's something rotten in the state of whatever field or community you are looking at. Janet again:

I do not think we can afford to embrace resignation here. I think that seeing the problems actually saddles us with some responsibilty to do something about them. [...] I don't think we can have it both ways. I don't think we can trumpet the reliability of Science and wallow in cynicism about the actual people and institutional structures involved in the production of science.

I don't disagree, but I do wonder what actual somethings Janet has in mind for "us" to do. One of Janet's examples (of how we can't have it both ways) involves reproducibility of results:

[we can't claim] that reproducibility is a central feature of scientific knowledge [...] but [...] only the "important" findings will be tested for reproducibility in the course of trying to build new findings upon them

I don't think this is actually a problem. Very little research is reproduced; most is confirmed or corroborated by means of further experiments predicated on the assumption that the original result is/was reliable.

If a result is false but never found out, it probably means no one cared. It's not as though people were combing through the original research literature and changing their lives or doing dangerous things on the basis of what they find there. (Or are they? If so, someone alert the Darwin Awards people.) If no one ever predicates a further experiment on a particular result, that result was presumably entirely uninteresting. I don't think that "a whole lot of findings on the books but not fully verified" is a problem -- the "books" are not running out of room, and the potentially useful findings will be verified or refuted precisely because they are potentially useful.

This, though:

when scientists report that their serious efforts to reproduce a finding have failed the journal editors and university administrators can be counted on to do very little to recognize that the original finding shouldn't be counted as "knowledge" anymore

is an entirely different kettle of fish -- rotten fish at that -- but you can't blame it on the scientific method. It's the scientific infrastructure that's the problem here: [publish or perish] x [shrinking funding] x [far more scientists than permanent positions] = powerful incentive to cut corners or outright cheat, and very little incentive -- even for those with tenure and power -- to stand up to the cheats or take the corner-cutters to task. When what should happen in response to irreproducible results does not happen, that's politics -- not science.

In a similar vein, Janet says:

I don't think we can proclaim that scientific work is basically trustworthy while also saying everyone has doubts about his collaborators [...], and it's a completely normal and expected thing for scientists to present their findings as much more certain and important than they are...

Again, I think the system works -- that is, scientific findings are generally reliable, for reasons of confirmation/corroboration as above. The larger question, though, is, does it work as well as it could? Here I think the answer is a resounding No, at least from the perspective of a working scientist. The system is a meatgrinder, and if you want to come out whole at the other end then things like not overselling your results become luxuries you can't afford.

That's not to say that there won't always, so long as funding has any limits on it at all, be corner-cutters, cheats, overselling of results (particularly to granting committees), and so on. What we have now, though, is a situation in which there are so many more postdocs than research positions to which they might aspire that it is hardly to be wondered at that "normal misbehaviour" does not seem an oxymoron.

When more than 75% of postdocs (and that figure is five years old, and I can't see it having dropped in that time!) will not go on to any kind of permanent research position, we are not talking about the kind of competition that selects the best individuals and ensures the best product. We are talking about a situation in which advancement is more dependent on personal politics and luck than on talent or hard work. Working harder won't give you an edge -- the guy in the next lab sleeps there. Being smart won't do it -- the average IQ where you work qualifies for MENSA. Being willing to cheat, though -- if you don't get caught, that might just help.

Janet goes on to say:

I do think that scientists who care about building good scientific knowledge have some responsibilities to shoulder here.

How do you behave in conducting and reporting your research, and in your work with collaborators and your interactions with competitors? In a community of science where everyone behaved as you do, would it be easier or harder to open a journal and find a credible report? Would it be easier or harder for scientists in a field to get to the bottom of a difficult scientific question?

What kind of behavior do you tolerate in your scientific colleagues? What kind of behavior do you encourage? Do you give other scientists a hard time for doing things that undermine your ability to trust scientific findings or other scientists in the community? If you don't, why not?

These are all very good questions, but it's that last one that gets to the heart of the matter. I do what I can -- I don't cheat or cut corners or steal, and if everyone did as I do the credibility of published research would improve, and it would be easier for scientists to do their work (in particular, given my support for Open Science, collaboration would be much easier).

If that sounds like blowing my own trumpet, it's not: I'm a lowly postdoc, and what I said of myself is probably true of the majority of scientists at or below my level on the food chain. It's also why I am likely to remain a lowly postdoc until I become unemployable in research: those who go on to be PIs and Department Heads and Directors of Institutes are largely those type-A assholes who are willing to cut corners and stomp on other people to get what they want. How exactly am I supposed to give a PI "a hard time"? If I don't, I think it's pretty damn clear why not. (You -- anyone reading this -- can think less of me for that if you wish, but since I doubt that you are one of the rare few who has put their own, and their families', livelihood on the line for a principle, you can also blow me.) I can, and do, discuss these issues with other postdocs -- but to what avail? It's precisely the ones who don't listen, who secretly think me naive or weak, who are going to have the competitive edge.

Janet ends by saying:

maybe it's time to turn from cynicism to righteous anger, to exert some peer pressure (and some personal discipline) so that hardly anyone will feel comfortable trying to get away with the stuff "everyone" does now.

Well, I'm full of anger. It doesn't seem to be helping anything.

Rob Knop is in a jam all too familiar to researchers and their long-suffering loved ones. He's on the tenure track, but he doesn't have independent funding -- and so his university is basically planning to kick him out:

Vanderbilt has made it 100% clear that without funding at the level of an NSF grant, I will not get tenure, regardless of anything else. Indeed, my chair has told me that funding is the only issue he sees as being a serious question with my tenure case.

Note that Rob is clearly a sufficiently good teacher and colleague, and his scientific acumen is clearly sufficiently well regarded, for him to be granted tenure -- which is the only form of job security available in academic research. Still, he's a goner if he doesn't make that funding cut -- which, these days, somewhere between 10 and 20% of applications do, depending on field and political climate.

The system is broken: there are too many PhD graduates and not enough real jobs for them. A postdoc is not a real job; even a tenure-track position, one step up the foodchain from a postdoc, is not a real job. A real job will not be yanked out from under you every few years, unless you or your boss can continually win funding -- and when you get down to 20% funding levels, between politics and the sheer volume of work dumped on the granting committees, you might as well pick the names out of a hat. A real job does not leave you entirely at the mercy of your superiors, who can demand insane work hours from you, knowing that if you won't sacrifice your life on the altar of their lab/department/whatever, there are ten other PhDs clamoring for the chance to do so. I'm no fan of the dismal science, but the law of supply and demand does seem to be consistent with observed phenomena here.

There have been a number of responses to Rob's cri de coeur, and if you're interested in the issue Google blogsearch and Technorati (if it's working) will find them for you. I have been collecting links on the "postdoc problem", and meaning to look for actual data on same, for some time -- maybe I'll even write that post one day. For now I just want to grab one sentence out of Chad's response:

I've been extremely fortunate in my career.

And this is key. The majority of successful (tenured, funded) academics got that way largely by luck. Most of them have all kinds of fairy tales, as Rob puts it, that they tell themselves so that they can believe it was talent and hard work and nothing else, which is why they continue to urge smart kids into dead-end "careers". (I do not mean to imply that Chad is untalented and lazy! The point here is that he is one of the few who recognizes what he owes to dumb luck.)

You cannot bank on luck.

I'm not saying "don't ever go to grad school, don't ever try to make a living out of research" -- research is addictive, just look at me, still kidding myself I have more than a year or two left. But I am saying "you probably won't make it", by which I mean "have a backup plan".

For my own field, biomed research, I would encourage would-be grad students to consider medical school instead. You can do basic or clinical research with an MD, and you have a backup career (a real career, not ten years of indentured servitude as a postdoc followed by "tough, yer out"). Hell, if you're really keen you can do an MD-PhD -- although frankly I don't see the point. You learn nothing about research in a PhD that you can't learn on the job, and it's not as though you're going to go straight from school to running a lab. You'll be serving a kind of apprenticeship, a sort of postdoc, in any case -- but you'll be treated better. (There's a widespread perception among PhDs that MDs make lousy researchers, but no one ever presents any hard data and my own experience indicates that the proportion of idiots is the same among MDs and PhDs -- roughly 90%, as per Sturgeon's Law.)

In case anyone was wondering, this is the sort of thing I do all day. That cotton-candy-looking stuff is mouse genomic DNA, about 600 micrograms of it, harvested from a tumor caused (we're trying to find out how) by deletion of the MNT gene in T cells. I was going to try to say something profound, but the little DNA monster (the "eyes" are air bubbles trapped when the DNA came out of solution) rather deflated my pomposity.

What's here? Why, the first-ever Science Blogging Anthology, of course: 50 posts, plus a couple of bonus entries, chosen from the best of science blogging in 2006. There's also a preface and introduction by the editor, Bora Zivkovic of A Blog Around The Clock.

I was privileged to help Bora narrow the field from well over 200 posts, and many of my favorites made it into the final 50. As Bora intimates in his introduction, blogs are conversations and so they lose a certain liveliness when embalmed in a blook (blog + book; don't blame me, I didn't coin it!) like this. Nonetheless, there is some excellent writing in this thing, it is as perfect an introduction to science blogging as you're likely to see offline, and it's a fun read all on its own. True to the open nature of the original medium, you can of course surf over to Bora's blog and find the anthology entries listed there. No one will mind if you do, but I hope you will also consider buying the blook -- which, after all, unlike the internets, you can carry with you on the bus and leave on the break-room table at work (which is what I plan to do with my second copy). It's priced at cost and any incidental proceeds will go towards next year's edition.

Bravo, Bora!

New(ish) bioethics blog Biopolitical Times has a post up which takes issue with PZ Myers' response to the proposal to carry out therapeutic cloning using enucleated cow eggs and human somatic nuclei. Myers:

In fact, I want to go further than these scientists propose.

Don't terminate the experiment after a few days when you've got healthy, growing blastocysts. Slip the best looking ones back into the cow. Work out methods for gestating them in a non-human mammal.

I want to be there nine months later when the vet reaches into the cow's vagina and pulls out a slick, slimy, healthy human infant.

I want to see the Pope's head explode when he sees it. I want David Cronenberg there with a camera, cackling happily.

Jesse at BT:

All this is proposed to rile up cultural conservatives, whom the blogger ridicules. Speaking as a generally secular political progressive, this attitude frightens and frustrates me. I've long felt that embracing the worst aspects of human biotechnology, such as these "Brave New World" scenarios, is a short road for progressives to lose sight of their core values and alienate the majority of the public. Rubbing this in the faces of those who are opposed - a group much larger than religious conservatives - for the purpose of a "fun and exciting" discussion is adolescent.

Now, I think Myers is trying to be funny. It's impossible to tell, of course, because mixed in with what might pass for humor is his usual brand of vicious elitism and kneejerk prejudice.

The thing to remember about Myers is that, as I've noted before, he's not a scientist (ask PubMed), nor is he an ethicist. He's just a loudmouth braying into the cozy echo chamber of his blog. Best to ignore him, except that I feel obligated to push back from time to time just in case real people ("Joe Sixpack", as Myers would have it) start mistaking him for a spokesman for actual research.

Further to the petition and boycott pledge I linked a while back, Tom Stafford has put together an open letter to Reed Elsevier that you can sign if you are an academic or researcher. Tom writes:

The letter will be sent to the Times Higher Education Supplement, a leading UK academics' weekly, with potential for other national and international coverage. This will be the next in what has now become a series of open letters from professional users of Reed products. Previous letters have been signed by medics (in The Lancet) and high-profile writers (in the Times Literary Supplement), and both have received considerable, and worldwide, media attention.

Here's the text of the letter (also available as a pdf here):

Mr Jan Hommen
Reed Elsevier PLC
1-3 Strand
London
WC2N 5JR

xx October 2006

Dear Mr Hommen

ARMS FAIRS AND ACADEMICS

We are an international group of academics who are extremely concerned
about Reed Elsevier's involvement in organising major arms fairs in the
UK and around the world.

We rely on our academic work to be disseminated chiefly by means of
books and peer-reviewed articles, a significant share of these via Reed
Elsevier publications. Being both contributors and (unpaid) referees,
and readers of Reed Elsevier journals makes us stakeholders in the Reed
Elsevier business.

On its website, your company states that it is "committed to making
genuine contributions to the science and health communities" and that it
is "proud to be part of [these] communities". Conversely, we are not
proud to be associated with Reed Elsevier as we feel your statements are
undermined by the conflict between your arms fair activities and our own
ethical stance. Arms fairs, marketing the tools of violence, are a major
link in the chain of the global arms trade which proliferates arms
around the world and fuels a cycle of human, scientific, economic and
cultural destruction.

This is entirely at odds with the ethical and social obligations we have
to promote the beneficial applications of our work and prevent their
misuse, to anticipate and evaluate the possible unintended consequences
of scientific and technological developments, and to consider at all
times the moral responsibility we carry for our work.

We call on Reed Elsevier to cease all involvement in arms fairs since it
is not compatible with the aims of many of your stakeholders.

Yours sincerely

[Signatories]

If you want to sign it, send email to tDOTstaffordATsheffieldDOTacDOTuk with "open letter to Reed Elsevier" in the subject line and a brief note including your full academic title, name, discipline and institution (or former institution if retired). The petition is ongoing, so also please sign that if you haven't already. As I write there are 357 signatories; if you're reading this you will probably recognize #19, 32, 55 and 90 (I'm #28).

I know that, after the umpteenth petition or letter or fundraiser or whatever, outrage fatigue starts to set in; and I know that, as world affairs go, there are more important issues than scumbags Reed Elsevier branching out into arms dealing. But -- and here I'm speaking to my colleagues: researchers, teachers and academics the world over -- this is our issue. It's in our professional backyard; we own a chunk of it. Not only is a major academic publishing house part of our community, or at least of its infrastructure (whether we like it or not), but as the primary consumers of their primary products and services we have an unusual degree of leverage in this situation. Reed Elsevier is a business: if enough of their customers sign Tom's letter and petition (and Nick's boycott), they will get out of the arms trade.

In the course of promoting next year's Science Blogging Conference, Coturnix writes:

Jean-Claude Bradley is the pioneer in the use of blogs in science in the way that too many of us are still too scared to do - posting on a daily basis the ideas, methods and data from the lab.

Not all of us are scared. I have colleagues with legitimate claims on all of the work I am doing at the moment, and none of them are willing to go to open-notebook. I anticipate even having trouble with my refusal to deal with Elsevier and my intention to publish only in open-access journals.

I've been in this lab a year, so everything I'm doing is directly based on someone else's data and ideas -- that is, to such an extent that I do not feel I can insist on an open notebook. Recently, though, I applied for funding to start an entirely new project. This will not mean that I can suddenly ignore my colleagues' wishes, but it will put me in a stronger position to say, "well, this is my project, and I want to do it this way".

I think of it as just another experiment. If I'm right, open science is a better way to work, and the benefits of choosing a better model will become apparent to my colleagues, and so open science will spread from early adopters like Jean-Claude (and, soon, I hope, me). If I'm wrong, I'll fail -- but I'll fail on my own terms, and I can live with that.

Lab meetings are an unavoidable part of lab life. I've worked or studied in seven labs in two countries, and in all of them a regular, usually weekly, meeting was part of normal lab function; I'd venture to say that it's pretty much a universal. The format doesn't change much from lab to lab, either. The "body" of the meeting consists of either everyone presenting a quick rundown of what they've been doing, or one person presenting their latest work in more detail, and general lab business is an "anyone got anything?" sort of affair tacked on at the beginning or end. No one has a defined role, there is no agenda, no records are kept. And then, of course, everyone complains about wasting time in lab meeting.

This entry was prompted by our (Hurlin lab) meeting on Friday, where we complained about wasting time and talked about ways to improve our meetings. It struck me that if you're going to do something 50-odd times a year, you might as well get good at it, and with our meeting format currently being overhauled this is the perfect chance for me to try things out. I'm going to go over this with the spousal unit, who is something of an organization junkie/expert, and I'm hoping that the Lazyweb will chime in as well. I'd be very interested to hear about what works, or doesn't work, in your lab meetings.

So why do we even have lab meetings? There seem to be three basic functions -- that is, three things we want to achieve. First, it's a chance to get everyone together for announcements, organization and joint decisions: do we need more gel rigs, who's going to be the new safety officer, that kind of thing. Second, it's a way to keep everyone, particularly the PI, in touch with everyone's projects. Finally, it's a way to get everyone's feedback on your project and any problems you might be having -- to get the combined lab brainpower focused on one question or set of questions.

Most of the information on the web relates to (*shudder*) corporate meetings, but I've picked out the bits I thought were applicable to lab meetings. Fwiw, here are most of the sites I used to put this list together.

1. Make sure you need a meeting.
Given the functions I listed above, we need the meetings, but perhaps not weekly? Would monthly be too infrequent? What about every two weeks? It probably depends on the size of the lab and how much time the PI spends actually in it, but for most labs I guess weekly meetings are best. Also, should we try to accomodate all three functions in one meeting, or would we be better off splitting the "admin" and "research" functions? Since "admin" doesn't usually take much time, I think the fewer meetings the better.

2. Start on time and end on time.
Nearly every site I read emphasizes these two points, and that timekeeping is crucial. Another common suggestion is to give people defined roles, including facilitator (see below) and timekeeper. In small meetings, I guess these two roles could be combined, but there might be benefit in keeping them separate.

The question this raises for me is, how long should a lab meeting be? Ours start at 09:30 and can easily stretch until 12:00, which more or less wipes out half a day. I think lab business should take no more than 20 minutes (and often much less), which leaves presentations. One way to get them down to a more reasonable time might be to make them a bit less informal than we currently do (photocopied pages out of someone's lab notes are not uncommon!). If the presentations were more structured, they could more easily adhere to a time limit. I think I'll suggest that it shouldn't take more than 30 minutes to present your last 6 weeks' worth of work, especially if you focus on questions you want answered by the lab Hive Mind. Supposing that questions and discussion take up a full hour, that's still a two hour meeting.

3. Have an agenda.
For a lab meeting, I think this means something more like set a format:

• Lab business first or last? (Last, so there's incentive not to drag it out. We currently do it first, and tend to yap.)


• Who will speak?-- one person at a time, or several, or everybody? I think this depends on the size of the lab. We have 6 people, so if only one person speaks we each present every 6 weeks. I think this is about right, but some of my coworkers would like to get the Hive Mind's and Peter's undivided attention more often.


• Should each presenter follow a general outline, so that talks have a structure? As above, I think so -- it will help keep the presenter and the meeting focused on what we're trying to achieve. I think I'll suggest something along the lines of: background (what project is this again?), current results, problems, future plans.

4. Keep minutes.
Another nearly universal recommendation. Minutes can be used to start the meeting with action items from last meeting, which can be useful to nudge people along with their commitments. (In the same vein, action items should always come with an attached Person Responsible.) Minutes should be archived in a communal place (like our shared disc drive), so that everyone can refer back and you don't have to keep reinventing the wheel. Keeper-of-the-Minutes is another role, like timekeeper and facilitator, that needs to be assigned or rotated.

5. End the meeting with a summary.
Mostly for lab business: what are we going to do? Who is going to do it?

6. Get feedback on whether the format is working.
We'll be experimenting with these ideas over the next few months, so it will be important to keep track of what's working. (I'll report back here.)

7. Facilitation is crucial.
Universally acknowledged, and may well be the most important point. Having someone to keep everything on track seems to be critical for what I am trying to achieve here: avoiding timewasting. Some ideas that seem good to me:

• the facilitator shouldn't take sides on an issue, but strive to find out what the consensus is (may be difficult in small meetings)


• the role of facilitator could be rotated around, so everyone shares the task (and if someone should prove to be especially good at it, they could take it up permanently)


• a good way to avoid sidetracks is to have a sheet of paper or whiteboard on which to "park" deferred topics


• a good way to encourage lurkers and dampen the dominant is to go round-robin and get everyone's feedback as a way of finalizing a topic

So, that's my first pass at improving lab meetings. Any ideas, Lazyweb?

Rob Helpy Chalk is a philosopher and a teacher and has a brain approximately the size of a planet (note: not a pluton), so I am very pleased to see that he's interested in scientific communication. I'll weigh in on his ideas later, when I have some time, but I'm posting this now to alert people I think will be interested. If you read me at all, you will probably be interested in Rob's thoughts on scientific communication and I'd really like it if you'd take a look at the linked post and give Rob some feedback. This has all the makings of a fun, useful conversation.

Comments are off here, go talk to Rob. Mind you don't put links in your comments though, his spam filter has got teeth. The comment I tried to post is below the cut; I'll wait until tomorrow and try again if it still hasn't appeared. it's now up at Rob's post. PZ Myers' comment thread also has some good stuff.

Update: Arunn of Nonoscience has put together an alternative chart and generated even more good discussion.

more...

Dammit, I (re)started this blog to talk about science, and I'm gonna talk about science!

Over at JOHO/blog, Dave is posting summaries of the talks he attends at Foocamp06. This one really pushed my buttons:

Chris Csikszentmihalyi says science doesn't work the way it thinks it does. For one thing, only 3-5% of experiments are re-proven. Often that's because they're so sensitive to instruments and materials. Also, much of the knowledge is tacit. Instead, scientific conflicts are usually settled by looking at the lab it came from, etc.

OK, let's unpack that a little:

science doesn't work the way it thinks it does.

Having just read Structure of Scientific Revolutions, I'm inclined to think this is true. However:

For one thing, only 3-5% of experiments are re-proven.

Where'd he get these numbers? This recent article (not freely available, brief summary and discussion here) shows that, of 19 papers in an apparently-randomly-chosen issue of Nature, 17 reported results that have been corroborated within four years. My own informal efforts seem to agree that a majority of results are "re-proven", for meaningful values of "re-proven". If CC is talking only about straight replication (same experiment, different hands) he's simply bypassing the more common mechanisms by which scientific results are established as reliable.

As for mechanism:

Often that's because they're so sensitive to instruments and materials. Also, much of the knowledge is tacit.

The article I linked talks about this --

[on] recreating an exact copy of a piece of experimental kit: "It's very difficult to make a carbon copy. You can make a near one, but if it turns out that what is critical is the way he glued his transducers, and he forgets to tell you that the technician always puts a copy of Physical Review on top of them for weight, well, it could make all the difference."

True, but let's not forget that ratio (17/19). This is exactly why most results are corroborated (shown to be reliable by work that builds on them) rather than directly reproduced. Well, actually, the more basic reason why is that scientists tend to trust published data, with good reason (fraud is real but not common¹) -- why waste time repeating an experiment that shows X when you can test X just as well, and move your own work forward at the same time, by designing an experiment to build on X? Unless X is thoroughly outrageous/counterintuitive/whatever, that's what most researchers do: assume that published results will stand up. If the odds are 17/19, I'd call that a pretty fair bet. If CC were right, and the odds were more like 95/5, wouldn't science have long since ground to a halt?

Then there's this:

The Prayer Gauge Debate. In the 19th Century there were attempts to measure the efficacy of prayer. Science went up against a popular paradigm. Chris contrasts this with lab press releases getting done if they promise a cure for cancer. I.e., scientists learn to mis-represent their projects in order to get funded.

See, that just chafes my scrote. Has CC ever tried to get an accurate representation of his work into the press? More to the point, has he ever watched helplessly as some PR flack mangled his research into a press release and made him look like an ass in the media? Scientists, as a matter of course, do not mis-represent their work to the media: they don't have to, the quality of science journalism being what it is. (They do, of course, tailor grant applications to the priorities of the funding bodies; the extent to which that practice approaches dishonesty is a different conversation altogether.)


----
¹ (though see here, particularly comments by per, for a different view)

OK people, when I talk about publishing data on blogs this is most emphatically NOT what I am looking for.

Words fail me. (Hat-tip blame: Chad.)

Dr Free-Ride has a good entry up about scientists and ethical behaviour. I have nothing to add to her basic point, which is that when ethics is seen as something imposed from outside, it is largely ignored; this idea will be entirely familiar to any researcher who has ever sat through the obligatory (!) ethics class or seminar or whatever their department requires.

Where I think Janet's discussion is missing something is in how to deal with this issue (and to be fair, she was mostly pointing out the problem, not trying to solve it):

To get "buy-in" from the scientists, they need to see how ethics are intimately connected to the job they're trying to get done. In other words, scientists need to understand how ethical conduct is essential to the project of doing science.

So OK, how exactly does that work? In a fairly straightforward sense, ethical conduct is demonstrably NOT essential to science or scientific progress. Science is being done now, often quite successfully (in terms of personal career advancement and, more importantly, in terms of real additions to the knowledge base), by unethical means. There is nothing about vivisection that makes it an inherently ineffective means of gathering information; many experiments that do not make it past IACUC would yield useful data. Further, if I successfully steal your ideas and publish them, I will have been doing science from the point of view of anyone (or anything, like the knowledge base itself) that doesn't know or doesn't care that I stole the ideas.

The trivial category here is unethical conduct like that of the Korean stem-cell team; this was dumb as well as wrong, because it produced bad data and was bound to be found out. The important category is unethical conduct that produces clean (useful, reproducible) data: what makes such conduct unethical, what aspect of its unethical nature makes it antithetical to doing science, and what is the mechanism of that opposition?

Within this category, we can distinguish between conduct that, if you get caught, will hamstring you within the scientific community (thieving) and conduct that, if you get caught, will cause the wider community to stop supporting you (vivisection). The key phrase here is "if you get caught"; that is, ethical judgement is community judgement. An individual cannot do much science without the scientific community; infrastructure needs alone make that clear. Neither, for even more obvious reasons, can the highly-specialized scientific community do anything without the support of the wider community. Unless you posit something like karma or divine retribution, I don't think you can find an unethical behaviour that both produces clean data AND is in and of itself "anti-scientific", that is, proof that ethical conduct is in and of itself essential to scientific progress -- unless, that is, you take into account the reliance of scientific research on community support.

In other words: what is ethical conduct? Whatever the community decides is ethical conduct. Why is ethical conduct essential to the project of doing science? Because community support is essential to that project.

I have, of course, sidestepped the larger question of HOW the community -- the scientific community, or society at large -- decides what constitutes ethical conduct. It's not true that vivisection is wrong only because if you get caught doing it your grant will be cut off (without anaesthesia, of course). Scientists are not just scientists, they are members of society at the same time. This is an enormous question, but a quick look at the scientific community will allow me to sketch my own view: why is it unethical for me to steal ideas? Because if everyone stole ideas, collaboration and other networks of trust would collapse. It's far more efficient to act in good faith and initially to assume the same of others. The same holds true for the wider community: whatever benefit I derive from someone else's disadvantage will eventually come back and bite me in the ass. On any but the short-term, immediate-future view, "do unto others as you would have them do unto you" is not a Divine Command but a sensible way to maximize one's own preferences.

Ah, Selva is wondering about something that has also been puzzling me:

For the past few weeks I have been in sneezing hell. Everyday when I wake up, my phlegm factory wakes up with me and kicks into high gear producing copious amounts of that white jelly that dribbles out of my nose (disgusting? Imagine what I feel..It's coming out of MY nose!) England has too many flowering plants. The damn pollen is killing me. Anyway, the question is: All the air borne irritants are present even while I sleep but I do not dribble when I sleep. Why? Why is that my nose runneth over only when am awaketh?

I, too, am afflicted with this yearly blight, this vile assault on my mucosae. Portland Anthophyta are trying to kill me; Satan has relocated his infernal Itch Factory to my nose.

On a bad (especially pollenaceous?) day, my nose and eyes begin to itch and run within moments of waking. Surely the offending gametes were present in the moments before I awoke: what part of the reaction requires consciousness? Conversely, what aspect of the sleep state prevents the physical manifestations of the allergic reaction? Now, sneezing being a reflex, it seems intuitively reasonable that it might be suppressed by sleep; although it seems less clear, itching might be a similar case¹. I'm also aware that the sinuses can produce mucus in one's sleep, as is anyone who's ever had a cold or 'flu. This is different: not only does the sneezing hold off while I'm asleep, but so does the snot. I sometimes wake with blocked sinuses, but never -- unlike when I have a cold -- with a runny nose. Once I'm awake, though, all bets are off and I have to make a run for the drug cabinet.

I have no idea what is going on, and would be most grateful if the lazy web could tell me. (A quick google reveals nothing of any use.)


¹ Mechanism, of course, is a whole nother can of worms in both cases. Is there a neurologist in the house?

Bora recently asked whether anyone was using Connotea. I am, and I like it fine. It's open source and has a web API, there's a lively dev forum, and it's continually improving. You could use any bookmarking service, like Simpy, to collect your science/work-related links, of course, but Connotea offers the compelling advantages of auto-discovery of relevant fields (DOI, author list and so on), an improving ability to play nice with reference manager software, and a more focused community with whom to share tags, bookmarks and ideas.

Now, much to my glee, Connotea has started actively supporting citations to blog entries:

A lot of you are increasingly bookmarking articles from personal blogs alongside traditional journal-published articles. In response to this, Connotea now has experimental support for treating bookmarked blog posts as citations, and it will automatically import publication data for those articles wherever possible.

Hot damn, says I! Of course I had to try it out, on the obvious test post. Here's a screenshot, with a regular PubMed entry for comparison: As you can see, Connotea correctly identified the blog, although it didn't grab the entry title (and I'm not the only one reading Science & Politics!).

This is the sort of thing that makes me feel that there really is an open science revolution underway. The internet is making possible real-time collaboration between large numbers of people with minimal regard to geography; as proprietary barriers to information flow are dismantled, this collaborative process can only accelerate and will, I believe, supplant traditional competitive models of research.

Dr Free-Ride linked to Zuska (Goddess of Science, Empress of Engineering, and Avenging Angel of Angry Women) talking about sexual harassment in science, in light of a recent study linking a sense of injustice among researchers to the probability that they will compromise their integrity. Zuska's Seven Scientific Commandments, paraphrased, are:

1. Do not rape your students and colleagues. No means no. Coercion is rape.
2. Don't engage in sexual harassment, either. If you don't know what that is, your university will have policies in place and people willing to explain them.
3. Er, that all goes for grad students too.
4. The points above all apply "even if you think she's willing or she wants it or she's asking for it or she needs it or whatever other excuse you come up with to put the agency on her and absolve yourself of guilt. They also apply even if she is actually willing."
5. Racial harassment? Also a no-no.
6. Don't steal ideas.
7. Don't steal ideas that have been published (that's plagiarism).

There's more to each point, including links, so do read the whole thing. Me, I continue to be astonished by my own naivete. I was aware that sexual harassment is a problem in science -- I've seen a few instances, and I'm even aware that I only saw most of those instances because the women involved stood up for themselves. But rape? Yes, rape. Zuska is serious. I am -- horrified.

Zuska, in turn, led me to Dr Shellie, who describes her blog as

...a year-long project to develop and articulate my opinions on the following themes, as they apply to my life and research:

• women in science
• how to improve the culture of science, particularly in academia
• societal benefits of science and technology

There's plenty to read in the couple of months Dr Shellie's been blogging, but just to continue the theme of this post for a moment, here's (part of) her take on women in science:

Making science departments more welcoming to women and minorities will result in a better working environment for everyone. Fortunately, a number of great initiatives are in place to do just this. Some of the main issues are to:

• Insure equal recognition for equal work.
• Encourage all students to actively participate in classroom activities in research, particularly talented students with low initial confidence.
• Value scientific contributions and content, not aggressiveness and self-confidence. Teach scientific communication skills and conflict resolution techniques.
• Promote role models for women and minorities in science and engineering.
• Work to accommodate dual-career issues and hiring concerns, which disproportionately affect women scientists.
• Develop university policies to accommodate childbirth and parental child-care responsibilities.

Again, there's more to each point than I'm copying here, including a good many links to resources and references, so go read the original post. I just want to focus for a moment on the first three points. There's nothing in those that is necessarily specific to women; that they apply more to women than men is a reflection of the general social disadvantage that affects women. Momentarily taking sex out of the language makes it clear that we are talking about a rising tide that will lift all boats: male and female scientists alike will benefit from changes in the culture of science that focus on rewarding merit and promoting cooperation. This is much the same as my usual "bottom line" argument in support of feminism: placing half of the population at a systematic disadvantage is a waste of human resources and a net loss for the population as a whole. Conversely, equality of opportunity across all demographics allows for the most efficient possible use of those human resources. It's clear that my interest in open science —

Anything to do with open access to source code, published information, raw data, &c. Blogs, wikis, databases, journals, anything that views information and information sharing as common goods or could be used to further that view. Also anything to put collaboration ahead of competition.

— has much in common with the interests and goals of feminist scientists.

In something of an aside to his reply to Abel's musings about a medical wikipedia, Orac makes a couple of good points about publishing hypotheses on blogs and the "scooping" issue:

[...]most cases of scooping aren't nearly as blatant as the one [PZ Myers described]. Most are a lot more subtle, and the vast majority don't involve any chicanery at all. Indeed, in my experience, most cases involve multiple labs working on the same question. In such cases, one of these groups will inevitably succeed at publishing their results first, and the rest will be "scooped," no dishonesty or using ideas or experimental protocols without appropriate attribution necessary. [...] (In fact, I wouldn't even call it getting "scooped.")

The Grey Area Problem, yes. (As an aside: I quite agree, being beaten to publication by legitimate methods is not the same thing as "being scooped" as I mean the term, though of course "scooped" is used both ways. Perhaps we need a better term for the despicable version.) My main point about grey areas is that their inevitability is not a dealbreaker: we have the tools and infrastructure to deal with them. Orac goes on to say:

In an ideal world, Bill Hooker's concept would be the way things should work and any hint that labs might be scooping each other would result in offers of collaboration, but that isn't always how things actually work.

The gentle implication of naivete is, of course, perfectly reasonable, and the realpolitik of the science tribe is already forcing me away from any strong position I might have started staking out (see, e.g., this).

Nonetheless, I think there's a place for the naive position, and I'd like to keep it around, even if only to mark a boundary -- "OK, fine, that's too much trust, but how close to that can we get?". Here's the thing: that's the way it does work with me. I won't ever steal an idea from you, and if we are interested in the same questions I'd much rather share the work and the credit between us than turn science into some bullshit macho game. If you want to be famous, go ahead and be the guy on TV if our work is important enough to get coverage -- I don't give a rat's. I just want to do science without running out of funds every year or two, and I don't see why I should have to claw my way past my colleagues into one of the increasingly scarce tenure track positions to do it.

A while back, there was some buzz about a study showing that, to quote the media reports, "Finger length predicts physically aggressive personalities". Like everyone else, I wondered what my finger length said about me.

You can get a pdf from here. The authors found that mean index finger:ring finger ratios were 0.947 (M) and 0.965 (F). Here's their method:

Scanning was conducted prior to examining or analyzing questionnaire scores. A Hewlett Packard Scan-jet 5400C was used to scan participants' hands. Before scanning, small marks were drawn on the basal creases of the index and ring fingers using a ballpoint pen by the first author. This was done to increase accuracy because it was difficult to see the creases clearly on the scans. Both of the participants' hands were scanned at the same time, palms down. Participants' index (2D) and ring (4D) fingers were measured from the hand scans using the GNU Image Manipulation Program (GIMP). The total length of each digit in units of pixels, from the middle of the basal crease to the tip of the finger, was determined using the GIMP "measure" tool. The first author took all of the measurements. Ratios were calculated by dividing the length, in pixels, of the second digit (index finger) by the length, in pixels, of the fourth digit (ring finger) for both hands. This technique provides good reliability (r = 0.98, d.f. = 8, P <0.01 blind test-retest of 10 individuals each scanned twice, with one week between the two scans).

I found that it wasn't at all difficult to see the creases on a scan (Epson Stylus CX7800, 300dpi), but choosing which crease to call the baseline is not entirely straightforward. I only scanned my right hand, as the authors found stronger sexual dimorphism on the right than on the left hand, and this is consistent with earlier literature:

Here's a closeup of the base of the fingers (ring on the left, index on the right):

See what I mean? Even if you draw a line with a pen, where do you draw it? You have to decide by eye: if you try folding the fingers towards the palm in an attempt to use the fold to direct the pen tip in some sort of objective manner, the skin is too loose to get a consistent result. Next, I drew lines on the crease closest my palm using the line tool in Photoshop, and delineated the end of each finger using the freehand lasso tool to identify the far edge:

So as to be readily visible on the web, that image shows a 2-pixel line, thinner than you could get with most pens, but for the actual measurements I used a 1-pixel line. I rotated the image until the finger axis was as nearly horizontal and the crease as nearly vertical as possible, then cropped from crease to end of finger; according to this method my ring finger is 885 pixels long and my index finger 902 pixels, giving me a ring:index an index:ring ratio of 0.981 1.02, higher than even the female average.

Or is it? The averages I quoted are from just one study, and even my brief attempt at a home-made replication shows that there could be significant measurement issues here. Further, whether or not my measurements and those averages are accurate, what does it all mean? How strongly does this particular morphological measurement correlate with, say, aggression; what's the proposed mechanism behind the correlation, and what other correlations might that predict?

Tune in next time (it's Sunday and I've been on the damn computer all day!) to watch one scientist (me) apply general principles of scientific reasoning to questions outside his own experience but (I hope) within his competence.

1. A comment on Pedro's post about Bora's post about scienceblogging led me to Stew, and reminded me about Postgenomic, which is Stew's creation. PG is a feed aggregator, but it's a feed aggregator with big ideas:

Postgenomic aggregates the feeds from life science blogs in order to do useful and interesting things with them. It's kind of like Technorati crossed with a really big hot papers meeting.

Its main uses - hopefully - are to:

• List the current top life science news stories and the hottest recent papers (or the papers most often cited by bloggers, anyway)
  
• Store and index reviews of papers
• Store and collate reports from conferences
• Help bloggers to share their expertise and, flipside of the same coin, to find useful papers on a given topic

[...]
Hopefully, as the site develops and the database grows the fourth point can be accomplished by organizing the papers by topic (perhaps using MeSH terms, or keywords, or the Technorati tags from the posts containing links to them). If you're looking for papers on, say, Bayesian networks in molecular biology but don't know where to start then you could fire up your browser, click on the appropriate tag in the Postgenomic index and be presented with a list of relevant papers and the blog posts that talk about them.

This is a great idea, and dovetails nicely with the current scienceblogconversation about what scienceblogging is, and what it might be good for. (You can add your blog to the postgenomic index by emailing Stew, and here are some ways to make sure the indexing goes smoothly.)

2. In the comment that sparked this post, Stew pointed to WebCite:

WebCite is an archiving system for webreferences (cited webpages and websites), which can be used by authors, editors, and publishers of scholarly papers and books, to ensure that cited webmaterial will remain available to readers in the future. If cited webreferences in journal articles, books etc. are not archived, future readers may encounter a "404 File Not Found" error when clicking on a cited URL.

A WebCite reference is an archived webcitation, and rather than linking to the live website (which can and probably will disappear in the future), authors of scholarly works will link to the archived WebCite copy on webcitation.org.

This not only provides a solution to the dead links problem,it also provides external timestamp authentication (which, as discussed elsewhere, is an issue when using blog posts to stake out academic/intellectual territory and avoid being scooped).

3. Stew found WebCite via Alf of HubLog. Alf discusses various solutions to the dead links/timestamp problem, including using Spurl (which is how I backup my Simpy archive) and his own cite bookmarklet. The bookmarklet allows you to grab a timestamped blockquote from another page, like so:

<blockquote cite="http://hublog.hubmed.org/archives/001243.html" title="HubLog: Creating a citable archive of a web page on Sat Apr 22 2006 15:59:48 GMT-0700 (Pacific Standard Time)>Academic papers or weblog posts often need to refer to external web pages; generally, you want people to see the external pages as they were when you wrote about them.

The simplest way to do this is a standard hyperlink, combined with a quote of the appropriate section of the text. If you're referencing long pages though, lots of lengthy quotes could get out of hand.</blockquote><cite><a href="http://hublog.hubmed.org/archives/001243.html">HubLog: Creating a citable archive of a web page</a></cite>.

Note: the original text included a link, which the bookmarklet doesn't preserve, but it's no big deal to add those back in (you could use "view selection source" if there were lots of links).

In comments below, Pedro Beltrao of Public Ramblings says:

What I disagree with is that we should go ahead and try to change things starting with the assumption of good faith. There is a percentage of people with bad intentions, this is clear, so we should plan for this. Open systems like wikipedia and digg are having problems and are taking steps to solve them. I suggest we keep an eye on these pioneering online social systems and see what solutions they come up with.

He's right, and it's an important point. When I said we should assume good faith, I wasn't clear. I didn't mean we should naively pretend there are no assholes in science. What I meant to convey was that, in addition to the sorts of measures we can learn from systems like wikipedia, we should do two things: 1, change the emphasis of the culture of science from suspicion to trust; and 2, have more faith in our ability to identify and deal with cases of bad faith as they arise. In other words, relax.

I think that we have good reason to approach fellow researchers as potential collaborators rather than potential scoopers (see below), and that when bad actors try to take advantage of that approach we also have, as a community and as individuals, the means to deal with them. When I say "the means to deal with them", I mean to include the sorts of checks and balances that Pedro is talking about.

Plentiful though they are, stories of scooping and other assholery are vastly outnumbered by the stories you don't hear, precisely because they are the stuff of every day:

• the PI who lent you her unsubmitted grant so you could copy the format for your own
• the postdoc who spent half a day digging through the -80 freezer to find the plasmid you wanted
• the NIH staff scientist who sent you transgenic fibroblasts in response to an out-of-the-blue email
• the paper you're an author on even though all you did was teach someone a technique they didn't end up needing¹ ("we said you'd be an author, so you're an author")

and so on and on. Those are all true examples from my own experience, and I'd like to invite readers to add their own in comments. It would be nice to hear about the up side of the scientific community for a change.


¹ I should clarify: an acknowledgement "for technical assistance" would have been more appropriate, and these days I would insist on that. At the time, I gave in and took the free ride. Mea culpa. I included the example just to point out that researchers are often generous even with that most precious commodity, publication credit.

There's a lot of great discussion going on at the moment about science blogging, the community of science, publishing and so on. I don't have time for a comprehensive roundup (though Bora's updates here cover most of it), but I want to quickly follow up on a comment that Abel Pharmboy made:

Bill Hooker was most vocal in Bora's comments and in a separate post at his own Open Reading Frame on how "scoopers" should be shunned by the scientific community.

(This was sort of tangential to the main point of his post, which is why I'm doing this here instead of in his comments.)

The point I want to make is this: for all my talk of shunning, and for all that I'm absolutely serious about increasing the risk associated with "anti-collegial behaviour" like scooping, I'm aware that we don't want to start a program of witch hunts. There will be grey areas, hard-to-prove cases, and we'll just have to err on the side of trust -- be scrupulous about "innocent until proven guilty". Better ten scoopers get away with it than one innocent be labelled a scooper. We don't have to catch 'em all, just associate a greater cost with the activity.

Further, it's not so much about punishing wrongdoers as altering community attitudes. Scientists now tend to shrug and say, "that's how the game is played" or some such -- as though that's how it HAD to be. Worse, people are not inclined to speak up and say, "Hey, I thought of that some time ago", because the response will be along the lines of "too bad, I published it so it's MINE ALL MINE bwahahaha!". If someone says to me, "Hey look, here's a blog post of mine outlining the central theme of your paper six months before you submitted it", I'm not going to say "tough luck". At the very least, I'm going to invite that person to work with me on questions we're both interested in, so we can publish together in future -- and more, I'd be happy to have my published work updated to give credit for their independent discovery. For one thing, how does it hurt me to admit that someone else also came up with "my" ideas? It amounts to a "note added in proof" if there are independent data involved, and a pretty ordinary courtesy if it's just about the concepts. Further, I don't WANT credit for something I didn't do, only for things I did do (and I don't even care so much about that, so long as interesting questions keep getting answered¹). If someone else came up with an idea or a result before I did, I want that known -- I'd feel like a fraud otherwise, if the community thought I was first but I knew otherwise.

In closing, let me just deal with one common objection to this idea of a more open system: that the world is full of assholes. Whenever I discuss openness, be it publishing data on blogs or being willing to share credit or listing one's bioreagents on BioRoot, I meet with a reaction that boils down to "what if someone takes advantage of me?". What if someone scoops me, what if someone fakes a blog post to get me to acknowledge them in a paper, what if someone keeps asking me for reagents and never gives any out? Well, to begin with it's a lot healthier (and, I'd argue, more productive in the long term) to start with an assumption of good faith than with the idea that everyone is out to cheat you. It's perfectly true that there will be assholes trying to take advantage, but here's the thing: they're doing that now, and the system we have is not hindering them much. In a more open system predicated on good faith interactions, assholery becomes harder to hide and get away with. As far as dealing with assholes as they appear, I return to a point from my last post: we're scientists, we present and evaluate evidence for a living. So if I'm going to accuse someone of scooping, for instance, I know -- it's my job to know -- what kind of evidence I need and how to get and present it. If I'm answering charges of assholery, I know what kind of evidence to demand, or to present in my defense. Give it a chance, I say: there aren't as many assholes as you think, and we already know how to cope with them.




¹ To the extent that I do care, it's a job security issue: my ability to win funding and get or keep jobs in science is largely dependent on getting credit for my discoveries. That (job security) is a common lament among researchers, and it's a function of the career structure/hierarchy, which is another problem for the community to deal with; for instance, there's an interesting discussion here. For now, let me just point out that a system in which everyone gets the credit they've earned, because everyone is willing to give it (as in my personal thought-experiment above), seems to me to offer more security than a dog-eat-dog system.

I've been posting pretty much nothing but verse, photos and linkdumps for a while now, partly because I've been exceedingly busy and, if I'm honest, mostly because serious original posts are a lot of work. The main reason, however, for the blog name change and the switch to my real name was that I want to start using this blog for talking about, thinking about, and even doing science, and recent posts by several other bloggers have prodded me into action.

I want to come back to issues and ideas raised by YoungFemaleScientist, Chad and Dr Free-Ride, but for today I'll mostly just point to Science and Politics.

Bora recently posted an elegant, scholarly, professional level discussion of Chossat's Effect in humans, complete with preliminary data, an hypothesis and an explicit request that the post be cited as a scientific communication; I noted this in a linklog and said he was helping to "usher in a new era of scientific publishing", and I wasn't kidding. I got online in about 1993, before there were blogs as we know them now, and my immediate reaction to this new medium was two-fold: "my people!" and "eee, publishing revolution!" I was right on the first count (even met the spousal unit online), and it's been slower than I'd have liked but I still think I was right on the second count as well. I'm not the first to observe that blogs are conversations, and conversations between scientists are where a lot of the creative action is; collaboration is a fun and powerful way to extend one's intellectual and practical reach. What better way to keep up with what's happening on relevant benches around the world than a well-connected network of lab weblogs (lablogs)?

Today, Bora has gone further with this idea. By way of answering the question "what are science blogs doing now?", he sets out a pretty comprehensive taxonomy of the current community. The category that interests me right now is "hypotheses and data", and I agree with Bora that there are two kinds of blog post in this category:

A) "This is my hypothesis and I am staking the territory here. I intend to test this hypothesis in the near future and you BETTER NOT try to scoop me!"
B) "This is my hypothesis, but I have no intention to follow it up with actual research. However, I'd love to see it tested. Please someone test it! And if you do, you will have to cite me in the list of references as your source for this hypothesis"

I would rewrite (A) to read: "This is my hypothesis and I plan to test it; if you can contribute, with ideas I haven't had or reagents I don't have or whatever it might be, great: let's collaborate. There's no need to steal when you can share."

Here we run into a personal bete noir of mine: "scooping". This means what it sounds like: taking advantage of someone else's work, to which the Scooper had advance (pre-publication) access by way of a conference presentation, visiting lecture, conversation, manuscript review, blog post or whatever, in order to slam a rapid publication into press ahead of the Scoopee, the person who actually had the idea. In Bora's comments, PZ Myers provides a personal example:

I got burned several years ago. I had a complete description of the protocols we were using in a teratology study, with some preliminary pictures of some of the results, all on the web. A few months later, my students found a paper published describing similar results in a fairly big name journal, and the protocols, which they had worked out by trial and error, were identical right down to the fraction of a percent of various reagents. It was damned obvious that they'd found our description and literally copied every step of our experiment...and there wasn't so much as an acknowledgment. The authors hadn't even bothered to contact us.

It was particularly galling to go to meetings afterwards and have people ask me, "Oh, so you're doing experiments like so-and-so?"

I've said elsewhere, I said in Bora's comments, and I'll say again: those assholes should be shunned. To do that to another researcher should basically mean the end of your career, by way of community opprobrium if not active sanction. I asked PZM what he did about his scoopage, and I'll be interested to hear his response. What typically happens is nothing: the scoopee shrugs and says something like "I couldn't prove they didn't think of it themselves, and it's too much trouble, and I don't want to rock the boat".

NNNNNNNGGGGGGGGHHHHHH!!! That galls me nearly as much as the initial assholery!

Of course, you don't want to smear "SCOOPER" all over an innocent researcher's reputation, and of course there will be grey areas and cases that are difficult to prove. But we are scientists, ferfucksake: we evaluate evidence for a living. It's what we do. Case in point: PZ lays out good-looking evidence of guilt in his comment, and as I said in reply:

As Bora points out, a blog post is a timestamped piece of evidence, a well-pissed-on territorial tree. It shouldn't take more than an hour or two with the lab books from the suspect lab to tell whether or not they stole your protocols -- unless they made up very careful fakes, which frankly would be more work than doing the damn experiments and not nearly as interesting.

You don't have to go screaming over to the offender's lab, punch him in the face and carve "SCUMBAG" into his forehead with a rusty scalpel. Simply contact the apparent scooper and lay out your evidence in a calm, straightforward manner. Frame it as an enquiry: my work shows considerable similarity to yours, how about we work together on some of these questions? If he blows you off, take it to the senior editor of the journal he published in; the journal has a vested interest in evaluating your claims, because they need a reputation for impartiality. While you're at it, cc: the apparent scooper's boss/es (dept head, dean of school, whatever). If you're wrong, that should become clear pretty damn fast -- and you haven't carved anything into anyone's face, so a sincere apology is all that's required. (Speaking for myself, if I were the innocent apparent scooper, at this point I'd be happy to talk about future collaborations, and possibly adding an acknowledgement about independent prior art to the paper in question.) If you're right, you may or may not get active satisfaction in terms of having the paper rescinded, or your name added to it, but you will have taken a stand against an unacceptable but all-too-common practice and, in doing so, nailed a big stanky turd to the scooper's reputation. Science, like all human endeavours, runs to a certain extent on reputation, so the mechanism is already in place to deal with this problem. The risk associated with scooping is currently very low; if you're willing to do it, you can probably get away with it. And there are always assholes in every field, so there will always be someone willing to do it. The good news is that collaborations are already CV fodder, in many cases regarded even more highly than individual efforts when it comes to promotions, grants and so on. We therefore do not need to raise the risk associated with scooping very high -- we can be absolutely scrupulous about proof, and about avoiding witch hunts -- before sharing becomes a more attractive option than stealing.

I guess everyone has now seen the story of the Turkish siblings who walk on all fours. If not, the media version is here (BBC story here), and this is a followup in which the whole affair begins, predictably, to degenerate into a circus. I say predictably because there was a strong whiff of rat about it from the beginning. The Turkish researcher who "discovered" the family, Uner Tan (see also, pdf), wants to name the syndrome after himself before the ink's dry on the initial descriptions. He's got one article in the mainstream journals, at the Int J Neurosci (subscription only and my library doesn't take it, if anyone reading this could send me a pdf I'd appreciate it); this is the abstract:

The author has discovered a new syndrome with quadrupedal gait, flexed head and body, primitive speech, severe mental retardation, and mild cerebellar signs with a disturbed conscious experience. This syndrome was exhibited by 5 of 19 children from a consanguineous family. The pedigree demonstrated a typical autosomal-recessive inheritance. The genetic nature of this syndrome suggests a backward stage in human evolution, which is most probably caused by a genetic mutation, rendering, in turn, the transition from quadrupedality to bipedality. This would then be consistent with theories of punctuated evolution. On the other hand, the extensor motor system causing a resistance of the body against the gravity may actually be subjected to evolutionary forces. This new syndrome may be used as a live model for human evolution. An accompanying video clip for this article is available as a downloadable file accompanying the official online version of International Journal of Neuroscience. To access it, click on the issue link for 116(3), then select this article. A download option appears at the bottom of this abstract.

I find the idea of a single mutation driving human evolution backwards from bipedality to quadrupedality literally incredible¹. It gets better -- Prof Dr Tan has also published an article (pdf) in Neuroquantology, which bills itself as "An Interdisciplinary Journal of Neuroscience and Quantum Physics". Here's that abstract:

The recently discovered "UNERTAN SYNDROME" consists of quadrupedal gait, severe mental retardation, and primitive language. This syndrome can be considered as devolution of human being, throwing a light into the transition from quadrupedality to bipedality with co-evolution of human mind. The genetic nature of this syndrome supports the punctuated evolution during transition from quadrupedality to bipedality. In light of Tan's psychomotor theory, accentuating the major role of the motor system in human mind, a new theory was suggested for the human evolution. Namely, the unique behavioral trait of man, the emergence of the habitual bipedality with Homo erectus (1.6 million and 250.000 tears ago) may be coupled with a resistive mind, which forced man to stand up against the gravitational forces with consequent success in tool making and hunting, using free hands for survival. The second stage in the evolution of modern human beings may be coupled with the emergence of language (circa 40.000 years ago), playing a major role in the origins of human mind.

Oooo-kay then. Enter Nicholas Humphrey and John Skoyles of the London School of Economics Centre for Philosophy of Natural and Social Science and Roger Keynes from Cambridge, who published an LSE "discussion paper" (pdf) (read: no peer review) on the family. According to that publication, "Tan contacted NH and JS, and together we visited the family in June 2005". Together, it seems, with a BBC documentary team; the film is scheduled for UK release next Friday. The Humphrey et al. dp is actually better than the Tan paper; in particular, it gives the lie to the latter's claim of "primitive language" by pointing out that all the affected siblings in fact speak Kurdish, though with difficulties. Nonetheless, it (the dp) smacks of the late unlamented Empire:

The local villagers laugh at and tease them. Because of this, the females tend to stay close to the house, but the male sometimes wanders for several kilometres. He helps raise money for his family by collecting cans and bottles, which he carries home in a pouch made from his shirt, held by his teeth. He is remarkably agile. We watched him moving easily across rough terrain in search of collectibles. While he searched ahead, his hands anticipated the contours of the rocks, so that he placed them deftly without looking down. He was able to run ahead of us, carrying his mouth bag -- while at the same time, to show off, he kicked one of his legs in the air (Fig. 2d).

Far worse than that, though, informed consent apparently consisted entirely of the following:

The father of the family signed a statement in Turkish which was explained to him by Defne Aruoba. In this statement he consented to his children undergoing medical and other tests related to research on their quadrupedal gait, said he understood that all information of relevance to their welfare would be shared with him, and acknowledged that he had no objections to the research being published. He signed a further statement for the BBC, consenting to film and photographs of his film of his family being broadcast.

The second world-science.net story above explains what's wrong with that:

"I'm suspicious all over the place," said Arthur L. Caplan, director of the University of Pennsylvania Center for Bioethics in Philadelphia. He said such a deal should have been pre-reviewed by one of the ethics panels that research institutions appoint for such purposes.

Humphrey wouldn't say whether that occurred. His two co-authors in the research project didn't answer emails.

Payments to research participants are normal, Caplan said, but must be vetted to ensure they're neither unfairly small, nor too large: "You're not supposed to bribe people into being subjects."

He added that participants should have advocates to advise them of their rights and the risks, such as the possibility that they might become subjects of a media circus. Humphrey's paper says a friend advised the family.

Michael Kalichman, director of the Research Ethics Program at the University of California, San Diego, wrote in an email that this sort of transaction generally "wouldn't be right in terms of the protection of research subjects and it certainly wouldn't be right in terms of the sharing of research knowledge."

Caplan is right to be suspicious, it's dodgy as hell. I hope some very pointed questions are going to be asked of the LSE about what sort of ethical oversight they provide their researchers.

There's one more paper available, this one from the Institut für Medizinische Genetik and published in the J Med Genet (abstract here, I could get the full text of this one). Mundlos' group show that the affected siblings' disorder maps to chromosome 17p, and -- on the flimsy basis that other heritable syndromes involving cerebellar hypoplasia do not result in quadrupedal locomotion -- speculate rather loosely about the evolution of bipedality. The authors themselves note that while the brain malformation is fully penetrant, two of seven affected walk upright, and that "we cannot exclude that early and sufficient treatment might have altered the outcome in the affected". It seems much more likely that the observed quadrupedal locomotion is a means of compensating for the cerebellar defect than a reversion to an ancestral state. There may be more clues to this issue available when the defect is more finely mapped -- we could, for instance, compare the affected gene/s between humans and other primates. The atavism hypothesis, however, will probably remain untestable since the affected gene/s are most likely to be involved in brain development and to not vary informatively between humans and other primates. That's a safer and saner prediction than "reverse evolution" (a stupid name that implies the existence of an identifiable "forward" direction), but it doesn't sell as well.

I wasn't going to blog about this, being content with a few comments at 3QD, but then Carl Zimmer removed his post about it. Carl pointed to the world-science.net story I linked above, which contains some back-and-forth between Tan and the LSE researchers about the ethical implications of payments made to the family. In comments, Humphrey objected, calling it "empty gossip". Carl pointed out that in fact it was the accusation of a professional colleague, not gossip, and raised other reasonable points, to which Humphrey apparently declined to respond in public. Here's Carl on his decision to delete the post:

Dr. Humphrey and I have been exchanging some email since then, from which I've gathered that some people--including some reporters--have misread what I wrote. They're under the impression that I reported ethical and financial hanky-panky going on. In fact, I was pointing out some ambiguities that raised my concern. When Dr. Humphrey provided me with information clarifying the situation, I immediately posted it. But that apparently has not prevented some people from carelessly misreading my post. I believe that serious ethical issues must be considered whenever scientists work closely with television productions. But I do not want to be involved in the spread of this sort of damaging misinformation, even passively. Given how things have devolved, it seems like tacking on additional explanations is not going to rectify the situation. So I've decided to delete my discussion of the topic. It's not a perfect solution, but it's the best I can think of.

That, then, is the actual point of my entry -- I wanted to comment on Carl's post, but I didn't think he'd appreciate my tone. I've provided the background above so that I can put it here:

Carl is not responsible for other people's misreading of his commentary, which I found eminently reasonable and which was not in the least unclear or confusing. I wish he hadn't deleted it, as I don't think it did Humphrey disservice, let alone damage. Moreover, few regular media outlets will give Humphrey the right of reply. Though I applaud Carl's concern for journalistic ethics, I think he is being too careful of the reputation -- or rather, the thin skin -- of someone who is discovering that the spotlight into which he eagerly scrambled is not always as much fun as he'd thought it would be.

----------
¹ It's not impossible, but if it turns out to be true my own amazement will be such good sauce that I will enjoy my helping of crow.

NASA produces a relatively steady stream of accomplishments which give me serious goosebumps. Earlier I pointed to Voyager reaching the limits of the known, and before that to the astonishing mission of Stardust. Now Stardust has completed that mission successfully, with its collection capsule, pictured at right, touching down safely and on target yesterday.

Think about it for a moment: seven years ago, the Stardust team launched a small robot into space, intending that it should travel 4,600,000,000 kilometers to rendezvous with a 15-km wide chunk of frozen dust travelling at more than 20,000 km/hr, photograph it, catch a thimbleful of its tail and then return that sample safely to earth -- and it worked. All of it. The little capsule (it weighs about 125 pounds) is safely in a NASA cleanroom, Stardust is on its way to a permanent orbit around the sun, and a few grams of space dust will be revealing some of the universe's secrets as the analyis (in which, incidentally, you can be involved if you want to) continues.

There aren't words for this feeling, there really aren't. Damn.

Sweet. Maybe I'm not too damn old after all. This National Center for Policy Analysis report stands in sharp contrast to (what seems to me) the constant flood of articles reminding me that Einstein was only 26 when he set physics on its collective ear, Gauss was 24 when he did much the same to mathematics, and so on. And on and on and bloody on. However:

The author analyzed data on Nobel Prize winners in Physics, Chemistry, Medicine, and Economics over the past 100 years and on outstanding technological innovations over the same period. He finds that:

• There is large variation in age -- 42 percent of innovations came about when their creators were in their 30s, while 40 percent occurred when the inventors were in their 40s, and 13 percent appeared when the inventors were over 50.
• In contrast, there were no great achievements produced by innovators before the age of 19 and only 7 percent were produced by innovators younger than 27.
• Controlling for nationality and field of study, the average age of a great innovator increased eight years over the past century.

Looking closer at the data, the author finds that:

• The upward trend for productive innovators is a result of a substantial decline in the innovative output of younger individuals.
• There appears to be no relative increase in innovation potential of those beyond middle age.

The article suggests that the average age is increasing, because the amount of knowledge has increased. Since thinkers must increasingly invest in acquiring intellectual capital and the accumulation of knowledge, the average age of innovation increases as well.

Any study which undermines the idea that "if you haven't thunk it by the time you're 30 you're not going to" is a friend of mine.

Update: Rob Carlson points to this article, which is short and well worth your time if you work with your brain. I don't think I agree with Rob that the article "take(s) seriously the myth that mathematicians and physicists do all their best work before the age of 40" -- in fact, I think the author, Ed Tenner, takes rather the opposite position. He does point out that many late-life intellectual achievers switched fields, moving away from the risk of stagnating among the ideas that brought them early prominence. This idea has about as much currency as the "dead by 40" one, but has a much more obvious mechanism behind it: one will always be tempted to cling to tools that have worked well, and success breeds paperwork. In any case, Rob is my pal: "most of the experimental scientists and engineers I know, including the majority of biologists I've run into, just get better with age." Damn straight!

Dear Mr Edward:

as a molecular biologist and an art lover, I am always pleased to see science informing art, and art informing the public about science. Your online exhibit, "Irradiance", is a wonderful example which brings the beauty and mystery of life on the smallest scales to a great many people who might otherwise never notice it. I am able to communicate something of the way I feel about my work by simply pointing to your art -- for which my thanks.

In light of the power of such art to shape public attitudes toward science, I write to ask you to consider a small change to the introductory text of your exhibit. You have included an explanatory paragraph regarding X-ray crystallography and a somewhat oblique reference to the infamous treatment of Franklin by Wilkins et al., so you are obviously familiar with Franklin's indispensable contribution to the discovery of the structure of DNA. It is somewhat surprising to me, then, that Franklin's name appears only in the titles of two of the "further reading" references you provide.

I think it likely, if unfortunate, that few people who see "Irradiance" will read the references. That being so, you miss an opportunity to put Franklin's name where it belongs: right alongside Watson and Crick in the public perception. I wonder if you would consider adjusting a sentence in your opening paragraph so as to include Rosalind Franklin's name? I believe that for you to do this would go some considerable way towards redressing that fifty-year-old injustice.

Sincerely,

Bill Hooker.

P.S. I should have pointed out -- I did notice that the text accompanying "Spiral II" includes a clear and concise explanation of Franklin's role. What I am suggesting is that her name also be visible on the very first page, to promote a sort of "brand recognition" if you will. --B.

The editors of the American Journal of Bioethics have a weblog, as anyone who has looked through my blogroll will know. Pace Mark Kleiman¹, bioethics is a vital field in all senses of the word. I take issue, however, with a recent comment by regular guest bloggers David Magnus and Arthur Kaplan -- a comment made not on the blog but in a newspaper column, and reprinted on the blog. If you haven't been following the Korean stem cell fiasco, this is an excellent primer.

Sirs --

in a recent opinion piece to which you linked in your blog, your colleagues David Magnus and Arthur Kaplan make the following comment:

When trust breaks down, the very possibility of science is threatened. That is why so much time is spent these days emphasizing to young scientists the importance of integrity.

I want to ask: emphasized by whom? Where? At no institute or school in which I have worked or studied (six, in two different countries) has ethics been more than an afterthought, a five-minute intranet "test" tacked on to requirements to satisfy the pesterers on the IRB. I have had mentors of great personal integrity, from whom I have learned, I hope, to conduct my own research in a manner deserving of the trust Magnus and Kaplan speak of; but I have also seen PIs work drunk and skirt the edges of data fabrication on a more or less routine basis. Martinson et al. held no surprises for me, as I am sure it did not for you or for Magnus and Kaplan. Science is just as "high-pressure, high-stakes and highly competitive" elsewhere as it is in Korea, and we can expect more scandals unless, as Magnus and Kaplan themselves put it, "training in ethical standards [is] seen as central to the enterprise of science, rather than burdensome make-work." To do this will indeed entail spending a great deal of time emphasizing to young scientists the importance of integrity. I would rather that high-profile ethicists such as Magnus and Kaplan not give the impression that this work is underway when, in my experience, it has barely begun across much of the scientific community.

----
¹ The comments on bioethics in this entry were uninformed, ill-mannered and, it must be added, uncharacteristic. Despite being called on it by hilzoy, I have yet to see Mr Kleiman attempt to justify his hostility. I got a server error trying to ping his entry, so I've emailed him.

Buried toward the end of this story about "the first real, honest-to-God, horny-making, body-shaking, equal-opportunity aphrodisiac", PT-141, is a little piece of behavioural research that I haven't seen mentioned anywhere else:

When Jim Pfaus tested PT-141 on his female rats, he based his experimental design partly on the work of Raul Paredes, a fellow rat sexologist testing the effects of something more elusive: personal autonomy. That’s a tricky thing to measure, but it can be done. Paredes did it like this: First, he looked at rat couples living in standard, box-shaped cages and recorded the details of their sexual behavior. Then, he altered the cages in only one particular: He divided them into two chambers with a clear wall broken only by one opening, too small for the males to get through but just right for the females. Architecturally it was a minor change, but what it did for the females was huge. It let them get away from the males whenever they chose to, and thereby made it entirely their choice whether to have sex. Paredes then observed the rats’ behavior in this altered setting. Here’s what he found: The effects of giving a female rat greater personal control over her sex life are essentially the same as those of giving her PT-141. Autonomy, in other words, is as real an aphrodisiac as any substance known to science.

The thing about PT-141 that's generating all the buzz is that, wonder of wonders, it makes women want to get busy. It's the first genuinely effective female aphrodisiac drug. Now, that's a wonderful thing and I'm not trying to say otherwise. All I am pointing out is that maybe it would also be a wonderful thing if we, as a society, were to explore the idea of personal autonomy as female aphrodisiac.

I really like Matthew Baldwin's site Tricks of the Trade, which is a repository for tips and hints that most of us would never think of, but that people in specific professions have come across. For instance, not long ago there was a tip about cat's whiskers and thin sectioning which I will be passing on to my colleagues at work (just as soon as I collect up a few of KC's whiskers).

I have to say, though, that the latest trick is just plain bad advice:

If there is a job announcement for a position you'd really like, but it's in another city, arrange your travel schedule so you "just happen to be in the neighborhood" prior to the application deadline. Set up an appointment to visit the department and pretend you don't know about the job opening.

Try your best, during the course of conversation, to get the department chair or someone influential to tell you about the new position and they'll probably suggest that you apply for it. Sound really interested, ask them what they're looking for, and make it seem that you never would have applied for the job if this person hadn't made this request of you.

For the price of an airline ticket, you've gone from "just a name" on an application to a familiar face that was personable and open to suggestions from faculty members. Also, the colleague who suggested the job to you will feel somewhat responsible to be sure your application gets considered attention.

It's a good thing for Barbara, who submitted this, that Matthew doesn't publish contact info or last names. This is advice to lie, plain and simple. It's worse than that: not only is it unethical advice, it's wrong and foolish. It's not at all common for strangers to "drop in" on a research department with whom they have no connection, even if the stranger in question is a scientist working in a similar field. It will trigger spidey-senses all over, and unless you're a much better actor than most people, the fact that you're visiting on false pretenses is going to be pretty obvious. Moreover, your chances of "dropping in" on "the department chair or someone influential" are approximately zero unless it's a fully-tenured position you're trying to sneak into. These are busy people. They probably won't suggest you apply for it, either, unless you've made it clear you're looking for a job -- in which case you've "blown your cover". Finally, suppose you do get the job -- you'll be working with people from whom you have to keep a secret, one about which you presumably, since you're the type to do this in the first place, feel pretty smug. How long before you screw yourself (don't think for a moment that faculty will forgive such a thing when your first tenure application comes around).

This may or may not be useful advice for other fields, but it's labelled "scientist" -- for which field it's frankly idiotic. If you want a job in science, just apply for it. If you're willing to pay for a plane ticket and put aside time to attend an interview, so much the better -- if you're at all an attractive candidate, that willingness will only push you further up the shortlist.

There's a thread over on Ask MetaFilter about idiosyncratic public restroom habits. As I knew they would, several public bathroom habits were identified as idiosyncratic which are in fact very sensible, and should be standard for everyone. I left a comment that I think is worth reproducing here (slightly edited for clarity):

Having worked in a number of hospitals, I've had the good fortune to be taught how to use a public restroom by a series of public health experts. That doesn't seem like something that you'd need to be taught, but for most people it is. Washing your hands properly (that is, the right way at the right time) is the single most effective thing you can do to protect your health and reduce infectious disease transmission rates.

The point about public restroom hygiene is not whether urine is sterile (it is, or should be), or whether you're breathing in teeny turdicles if you can smell someone else's leavings (you are). The point is that the restroom is a collecting node, a repository, a distribution center for "germs" -- bacteria, viruses, even dangerous protozoa, but most especially viruses (flu, rhinoviruses, coronaviruses, hepatitis A and more).

Here's the protocol I was taught:

1. Do your thing; cleaning of seats (and floors) is not entirely necessary, but it's a good idea to wipe up visible liquid. If the seat is dry, seat covers are reasonable insulation against whatever invisibles are still there. Likewise washing your hands first won't hurt, but isn't necessary unless you have something dire on them.

2. Wash your hands. Wash them properly -- most of you think you do this, and most of you don't. Use soap and water; do not use antibacterial anything; take at least as long to wash your hands as it takes you to sing "Twinkle Twinkle Little Star" in your head (or out loud, if you like). Use enough soap to get a good thick lather going. Wash the backs of your hands, wash between your fingers, do each finger individually, go up your wrist at least as far as where a watch sits, scrabble your fingertips in your palms to get under fingernails.

3. Rinse thoroughly -- use all the same motions.

4. Dry your hands. If there's a tap rather than an infrared sensor, elbow tap or foot pedal (preferred options all), then turn it on before you start washing and use a paper towel to turn it off. You'll probably want to use your second paper towel, since they're pretty flimsy and the first will probably be pretty well saturated (unless you frequent a better class of bog than I do). The object is not to touch any bathroom surface with your clean hands. All of those surfaces are trying to kill you. Use the paper towel to open the door, too.

Following this simple protocol is, seriously, the most important and effective thing you can do to improve public (and your) health. If everyone does this, infectious disease transmission rates will plummet. Don't just take my word for it:

The most important thing that you can do to keep from getting sick is to wash your hands. -- CDC's Natl Center for Infectious Diseases

Posters, videos, etc from the Natl Food Service Management Inst

Hand washing is the single most effective way to prevent the spread of infections. -- Canadian Center for Occ Health and Safety

washup.org, from the Am Soc Microbiol

Orac has a post up about MacGyver science -- you know, supercolliders made out of toilet rolls and chewing gum, or in this case an electrophoresis rig made out of kitchen stuff. Orac concludes, sadly, that it's not a practical way to cut lab costs. He's right, but there are good ways to cut lab costs.

(There are bad ways, too. I've done the grow-your-own Taq thing that RPM mentions in comments; it's not worth it. Too much fiddling and no one else in the lab will trust their experiments to your crappy enzyme anyway.)

For instance, commenter Dave raises a good point about resource pooling. A colleague of mine, lab manager in the last lab I worked in, estimated that he saved the lab about 30% of its running costs just by instituting a central ordering system. Once all orders went through him, he could shop around for best prices and pool orders with other labs to save on shipping. The institute that lab was in also saved itself a ton of money by putting together a central Store, so they could buy in bulk.

(A brief digression. It occurs to me that most of my tens of readers won't be familiar with what it costs to do biomed research. Quite apart from salaries, on-costs and infrastructure, I'd guess that most labs spend at least $500/month/staff member just on reagents and consumables (such as disposable plasticware). For a medium sized lab of five people, that's $30K per year. On top of that, costs vary widely from experiment to experiment; for instance, the lab I'm in now probably spends at least a further $20K/year on facilities for transgenic mice. If, like Orac, you do a lot of qRT-PCR, that's spendy too -- I think it goes close to $0.5/reaction and "a lot" is thousands of reactions per month, if not per week. To take a less fine-grained view, the average cost of an NIH grant (1992-96) was $274,710/year. Them's your dollars, taxpayers, so you should be keeping an eye on us -- in fact, there's a whole nother post -- hell, a whole nother career -- right there.)

Anyway, the whole point of this post is: there's another kind of resource pooling that is due for an internet-era upgrade: simple "hey have you got an antibody against X?" sharing. A while back, my current PI came up with the idea of a central database for sharing biological reagents; it's an idea best illustrated by example. (For non-scientists that is; labrats reading this will already be punching themselves and going "oh man why didn't I think of that, does it already exist, where is it gimme gimme gimme". Patience, I'll get to it.)

I happen to be interested at the moment in a protein called Smad3. We had an antibody to the molecule, but I also wanted to be able to distinguish between the phosphorylated (active) and non-phosphorylated (inactive) forms. You can buy an anti-phospho-Smad3 antibody, but it'll cost a bundle and you may be buying a lot more than you need. For instance, the one I linked comes in 40 µl lots for $110 (though most antibodies typically aren't sold in such small lots; the 100 µl/$250 size is much more usual). The company says that's enough for 4 blots, but I could probably stretch it to 40 -- if I wanted to run 40 blots, that is. Until I ran the first experiment, I didn't know whether I was going to pursue that line of inquiry, so I didn't want to toss 110 hard-earned taxpayer dollars (plus shipping and handling, and you really get screwed on that believe me) at something that might not pan out. (Plus, I wasn't too keen on the cross-reactivity with pSmad1, a related molecule, that the linked antibody displays.)

In such cases, and there are MANY, MANY such cases, what you typically do is wander forlornly around the building, asking if anyone has the antibody (or plasmid, or yeast strain, or oligo, or whatever it is) that you want. I did that -- even sent a couple of emails to groups elsewhere on campus -- but no luck. So I did the next thing you do, which is I ran a few searches and read a few papers, and discovered that there were a couple of antibodies in the literature that fit my requirements nicely. One of these was made in the lab of Prof Ed Leof at the Mayo Clinic; promisingly, it was cited in several papers by other groups ("the anti-pSmad3 antibody was a gift from Ed Leof"). So I sent Prof Leof email, and about 24 hours later someone in his lab sent me enough of his antibody for at least 100 blots (Prof Leof, Dr Edens -- if you're reading this, thanks again, and FYI the Ab can be re-used at least ten times, just put azide in the dilution buffer). All it cost our lab was FedEx shipping for a small container on dry ice.

Now, that's the way it's supposed to work -- and in fact, in my experience, the majority of such requests are met with similar collegiality and generosity. For myself, I am always pleased when I can help a colleague out. But here's the thing -- there's probably a lab right here on campus that has an antibody I could have used. I tried the obvious suspects (labs working on systems in which Smad3 might play a role), but even though they didn't have any I bet there's someone on campus who does. It's even likely that they bit the bullet and coughed up for the antibody on spec, and it's been sitting in their -80°C freezer since that first experiment didn't go the way they hoped. That shit happens all the time, ask any researcher. I want to emphasize that: this whole example, from me wanting something for just one look-see experiment to the likelihood that it was available on campus but I just couldn't find it, happens all the time.

Enter the idea whose time has come: an online database into which labs everywhere input the biological reagents they're willing to share: antibodies, plasmids, viruses, bacteria, yeast, mutant model animals, peptides, oligos, primer sets, cytokines, spendy chemicals -- the list of potential shareables is enormous and ever-expanding. Some of this functionality exists -- for instance if the mouse you want already exists, Jackson Labs probably has it or knows about it, and you can always do the literature thing like I did -- but it's scattered and inefficient. Think how much easier my quest for an anti-pSmad3 antibody would have been made by such a tool: one search and up comes a list of labs and antibodies, pick an antibody, sort the resulting labs by location, email (or walk over to) the nearest one. Here's another example: I have a new search going right now -- I want some Smad2/3-null mouse embryo fibroblasts and a set of Smad2/3 expression plasmids. I've sent out seven or eight emails to colleagues I found in the literature; I've had one negative and one positive response, but the positive response depends on permission from someone else from whom I'm still waiting to hear. I'm still not sure I'm bothering the right people, it's been almost a week (and Thanksgiving's coming up), and dammit there's probably someone in Portland, or maybe at the Hutch in Seattle, who has what I want and would share it with me.

See what I mean? Happens all the time. I want that database and I want it now! Peter suggested I make it happen, at least initially on a limited, local scale -- start with the six labs in our institute, then expand to include the whole OHSU campus. Great idea, so as a first step I googled around to see whether anyone had already done it -- turns out they have:

Welcome to BioRoot Bioinformatics
BioRoot is a non-profit organization dedicated to fostering communication, collaboration, and increased productivity in the biological sciences through information exchange.
We provide centralized databases to collect, store, and disseminate information about commonly used molecular biology reagents: antibodies, plasmids, strains, and oligonucleotides.
Use of these BioReagent databases will cut costs, save time, and accelerate research benefiting the bench scientist, the PI, and the public.

W00t!

The guy behind it is David Nix, who clearly has the programming chops to go from "an Excel spreadsheet uploaded to my web space somewhere", which is probably where I was going to start, to a fully-functional database complete with privacy/security measures. Major, major kudos, dude. (What is slightly odd is that I found out about BioRoot by googling, and found David the same way. Why haven't I heard of this everywhere? It's the best thing since PubMed, it should be huge. Apart from one subscriber-only article in The Scientist, I couldn't find anything.)

I've sent BioRoot an email, so we'll see how things work out. If it's what it looks like (and why wouldn't it be?), I'm going to become a hardcore BioRoot evangelist.

This is exceedingly cool:

SCIENTISTS have created "miracle mice" that can regenerate amputated limbs or damaged vital organs, making them able to recover from injuries that would kill or permanently disable normal animals.

The experimental animals are unique among mammals in their ability to regrow their heart, toes, joints and tail.

And when [fetal liver] cells from the test mouse are injected into ordinary mice, they too acquire the ability to regenerate [...]

As usual, though, there's a lot of important caveats missing from the "miracle mouse!" version of the story (and whenever you hear "miracle", especially in science, think of David Hume). The article to read is The scarless heart and the MRL mouse by Ellen Heber-Katz (who runs the lab responsible for most of these discoveries) et al.. It's a review article from about a year ago, so it doesn't cover the stem cell work, but it gives a good background. It's open source (but pdf, since the html version seems not to be working) and written for a fairly general audience.

The mouse strain in question is an inbred strain called MRL, and has been around since 1979. It was originally selected for large size and has a lymphocyte proliferative disorder which gives rise to a variety of immune problems, including autoimmune symptoms. For instance, the MRL mouse is a common model for systemic lupus erythematosus. The regenerative abilities of this mouse were discovered by researchers marking mice by punching small holes in their ears; within 30 days, the MRL mice healed the ear holes closed whereas other mice retain the holes for their lifetimes (mice live about two years).

Further investigation revealed that the MRL mice can regenerate almost all tissues except brain. This regenerative healing is fundamentally different from normal mammalian wound healing, and takes place without scar formation (which is of particular interest to cardiologists, since scars formed in response to heart injuries, including infarcts, are probably the primary cause of subsequent chronic heart disease and failure). Such healing is known in mammals, but only very early in development -- interestingly, prior to the development of certain immune, especially inflammatory, responses. Heber-Katz et al. report that T-cells from nonhealer mice do inhibit the ear wound closure response. It doesn't seem, however, that their immune dysfunction is the only mediator of the regenerative response in MRL mice. For instance, matrix metalloproteases 2 and 9 and their specific inhibitors have been shown to be differentially activated in healer vs. non-healer mice (MMPs and MMP inhibitors are primary players in tissue remodelling, including wound healing). In fact, at least 20 genetic loci (chromosome regions) have been shown to be involved in the MRL regenerative phenotype. Importantly, many of these show no overlap with the loci mapped to the autoimmune disorder. (In very plain English: it is not likely that the primary cause of the regenerative capacity is also the cause of the immune disorder, although there may be some overlap; this means that we may be able to replicate the regenerative ability without causing immune dysfunction.)

It is also not clear exactly which cells are doing the healing. In bone marrow transplant/transfer experiments, healing in both heart and ear tissue followed the recipient not the donor phenotype, meaning that bone marrow derived stem cells are not likely to be driving the healing response (although some involvement of donor cells was observed). Moreover, in these model systems recipient hematopoiesis is destroyed by X-ray exposure, so the cells responsible for the healing must be resistant to such treatment. It's also possible to reconstitute irradiated hematopoiesis using fetal liver cells, which contain a population of hematopoietic stem cells. Heber-Katz' group has tried that too (another open source article). The results were somewhat surprising: in the heart, healing followed the donor phenotype (i.e. the fetal liver cells transferred the regenerative capacity or lack thereof), whereas in ear injuries healing followed the recipient phenotype (as seen with bone marrow transplant/transfer). Once again, donor cells are seen in the healed heart but the mechanism of their involvment is not clear, nor is it clear why cardiac but not ear tissue could regenerate in this model.

Here's the thing that jumped out at me: because non-healer liver cells transferred that phenotype, it appears that scarring inhibits regeneration in mammals. In the MRL animals, something is holding back the formation of scar tissue, and (therefore??) regeneration is taking place. In non-healer mice which received healer fetal liver cells, high degrees of chimerism (~60-80%) were seen, whereas non-healer into healer transfers showed an average of only 12% chimerism. Why was 12% non-healer enough to cause normal healing and scarring in that transfer, but 20-40% non-healer was not enough to stop MRL-type healing without scarring in the reciprocal model? The authors offer one clue: "We do not know which cell population is responsible for [scarring with only 12% chimerism] and it may be different than the population that allows for a regenerative response in the reciprocal chimeras."

This much at least is already clear: the MRL mouse model will provide profound insights into mechanisms of wound healing (including the possibility of regenerative medicine) and the functions of hematopoietic stem cells.

If I'm going to delurk for lousy politics, I should also do it for amazing news that reminds me that there is still wonder in the world: Voyager has reached the edge of the solar system.

Eight-point-seven billion miles. Wow. Oh man. This is the feeling that got me into science in the first place.

(Image swiped from Voyager's home page, hat tip: GitM.)

I really must get back to writing about science. Here's a start: if you are a biologist, have much interest in evolutionary theory or are at all interested in the history of science, this charming eulogy for Ernst Mayr, replete with first-hand anecdotes, is a must-read. Don't miss the comment section either. Hat-tip: Brian Leiter.

This is gonna be so cool. (B-15A is 100 miles long, moving at about a mile per day; collision is expected no later than Jan 15.) (photo credit: NASA)

Update 050116: no collision information yet, but this site is probably the best one to keep checking.

Update 050119: aw poop. It ran aground. No boom. Still some amazing images though.

PZ Myers bemoans the lack of detailed knowledge of the history of biology endemic in the tech field, as revealed by the backstory of the Open Darwin mascot:

Once my platypus was chosen someone suggested that we use "Hexley" as the name of the new mascot since Darwin's assistant was named Hexley. It turns out we were wrong and the person we were referring to was actually Thomas Henry Huxley. Huxley was not Darwin's assistant but was a prominent English biologist in his own right. [...] By the time we found out our mistake "Hexley" had escaped into the ether and we felt that it was too late to change the name to "Huxley".

Quoth the good Professor:

Oooh. Ow. How embarrassingly ignorant. It’s bad enough that “someone” was so cavalier about the facts that they would toss out that misremembered rationale in the first place, but then for it to bounce around on a mailing list and no one noticed…ick.

Give me a break. Lack of information concerning one specialized field doesn't make someone working in an entirely different specialized field "embarrassingly ignorant". Whoever got Huxley's name and career wrong could no doubt reel off half a dozen names unknown to Prof Myers and sneer at him for his "embarrassing ignorance" too.

Then, in the next entry, one Sarah Ives finds herself labelled "credulous, bad [and] lazy" for "peddling lies to children" in this story.

According to the Bible, Noah was protecting the animals from a great flood. [...] some historians think Noah lived in the [Mt Ararat] area, if he in fact was a real man [...] Not everyone is convinced that McGivern and his group have found Noah's ark. There is still no proof that the ark exists.

(emphasis mine) The story includes a quote from McGivern, another from someone credible who thinks it's highly unlikely and another from someone just pointing out that the mountain in question is a bugger to climb. Granted the title is a bit sensationalistic, but where are the terrible, horrible, child-corrupting lies? I hardly think Ms Ives' piece qualifies as religious propaganda, however hard mention of his least favourite mythology makes Prof Myers' knee jerk.

As it happens, spousal unit and I have just taken up a subscription to National Geographic, partly because we were so pleased to see that the answer they gave to this question was a resounding and uncompromising NO. Thanks all the same, Professor, but we won't be cancelling anything just yet.

Update: (via Richard Chappell in the comments to PZM's thread) A few months after the article that has PZM (and now Brian Leiter) telling me to cancel my subscription, Nat Geo came down hard on the Arkspedition, calling it a publicity stunt and quoting a swarm of skeptics.

I must be missing something here. EurekAlert reports on a letter to Science by Richards Palmer and Lewontin review by Richard Palmer, thus:

Genetics aren't the only triggers for the traits a species develops, according to findings from a University of Alberta professor. The research challenges the classical Darwinian theory of evolution as being the sole explanation for how new life forms arise.

"Variations that do not initially have a genetic basis can still be important for evolution. They are 35 to 50 per cent as common as genetic variation, at least when it comes to the evolution of asymmetric forms" Dr. Palmer said. He was able to synthesize published evidence showing that the current 'genotype-precedes-phenotype' theory of evolution only explains about half of the examples he studied.

He came to his conclusions after reviewing more than 200 research papers from around the world, including a study on asymmetry (the difference between the left and right sides of the body) that was conducted using lobsters. Baby lobsters are born with two same-sized claws, but somehow, only one of the claws transforms into a larger crusher claw as the lobster grows. "The genetic program that makes a crusher claw is triggered by one claw being used more than the other. But if one side isn't stimulated enough, the program that makes a crusher claw never gets started. It's a clear example of how environment in some sense causes difference in form," Dr. Palmer said.

Further, studies on many other plant and animal species with both right-sided and left-sided forms showed that if two of the same 'handedness' were mated, half their offspring would be left-sided and half would be right-sided. "Genetics made no difference in the direction of asymmetry. It's a trait strictly determined by environment. From an evolutionary perspective, this means form arises first and the genes follow."

These observations have some parallels with modern medical research, Palmer said. "You can't say all diseases are gene-based. Consider cancer caused by asbestos exposure, or skin cancer. If you only study genetics, you would not learn much about environmentally-induced diseases."

What on earth? I can't get to the letter from home, so perhaps that will clear up my confusion when I read it at work tomorrow, but I'm not seeing anything there that conflicts with the standard model of evolution or indicates that "genes follow form". That last smacks of Lamarckism to me. The lobster inherited the genetic basis on which one or the other claw hypertrophies, and it's not hard to see how that would convey a selective advantage. The right- and left-sided forms inherited the basis of those forms; that the asymmetry distributes evenly among offspring of same-sided parents implies that the environmental triggers did not alter the genotype. Skin cancer and mesothelioma, when they are induced by environmental insult, arise from environmentally induced mutation: phenotype follows genotype. I'm looking forward to reading that letter.

Update: the letter from Palmer and response from Lewontin were a red herring, I just didn't see the review article when viewing the site without paid access. The EurekAlert article refers to this review by Palmer that appears to be, at least in part, bunk. Here's the abstract:

Because of its simplicity, the binary-switch nature of left-right asymmetry permits meaningful comparisons among many different organisms. Phylogenetic analyses of asymmetry variation, inheritance, and molecular mechanisms reveal unexpected insights into how development evolves. First, directional asymmetry, an evolutionary novelty, arose from nonheritable origins almost as often as from mutations, implying that genetic assimilation ("phenotype precedes genotype") is a common mode of evolution. Second, the molecular pathway directing hearts leftward—the nodal cascade—varies considerably among vertebrates (homology of form does not require homology of development) and was possibly co-opted from a preexisting asymmetrical chordate organ system. Finally, declining frequencies of spontaneous asymmetry reversal throughout vertebrate evolution suggest that heart development has become more canalized.

There's that "phenotype precedes genotype" thing again. Unless Palmer can propose a mechanism for that, I'm not going to believe it. I don't have time to read the thing properly now, so I'll do two things: call in reinforcements, and grab all the text and pics so I can read it at home. I'll say more when I've done that.

Update 041105: the cavalry arrived before I'd got around to reading the paper (I would have, honest, but the first page of the pdf wouldn't print out and -- eh, whatever). PZ Myers of Pharyngula has provided a good overview of the paper and background issues. I can add nothing to what he said, so -- what he said. Palmer does have a mechanism, and I do believe him. The concept of genetic assimilation has actually been around for quite some time, I just didn't know about it. (This makes no difference in re: my own ignorance, but that EurekAlert story was confused and confusing, a shining example of lousy science journalism. Read the paper or PZM's post and then the EurekAlert story again and you'll see what I mean.)

Walsby's square archaon has finally been isolated in pure culture, 25 years after its discovery in a pond near the Red Sea. This is a square microorganism (not a bacterium! you'd think news@Nature would get that right) found in hypersaline environments; the pure culture was isolated in medium containing 33% saline, which is about twice as salty as soy sauce. The trick was to use dilution culture to find a range of nutrient and salt concentrations in which the square archaon would out-compete contaminating species. Other square Archaea are known, but this one has eluded culture for so long, despite frequently being the dominant member of the halophile communities in which it's found, that its eventual "capture" is big news to a certain specialized group of microbiologists. Me, I just liked the pictures. Both belong to Mike Dyall-Smith, who led the group that isolated the elusive microcritter and has more information and images here. The top picture is a light microscope image (epifluorescence using acridine orange stain) and the bottom picture is an electron micrograph (bar = 1 micron, GV = gas vacuole, PHB = polyhydroxybutyrate).

Update: I forgot to mention that these things are not only square, they're very thin -- like teeny living tiles. I couldn't think why they would take that shape, so I asked Mike D-S (ain't email wonderful? I'm just some chump with a website, and I can bug a senior scientist half a world away -- and he takes time out to answer me). He says they contain bacteriorhodopsin, which is a light-driven proton pump that other Archaea use to harness the energy in sunlight. If this organism is doing the same thing, the shape makes sense as a way to maximise not only surface but also interior exposure to the sun. The gas vacuoles, then, might be a way of maintaining position at or near the water surface. (update 041018, stupid error fixed: s/photon/proton)

The verifier approach is Gordon Rugg's name for the method he used to investigate the 500-year-old mystery of the Voynich manuscript. Turns out the manuscript is probably a hoax, but that was really just a proof-of-concept for Rugg's method of mapping the work that has been done on a problem and locating the gaps in that map. He now has a host of new collaborators with whom to further test and refine the method; I will be watching with interest. If Rugg is right, he may have fathered a field which will alter the structure of the scientific endeavour and dramatically improve the way we think about and approach complex problems.

Student finds rare whale: I mention this story mainly because of one detail that annoyed me. Paleontology student Maggie Hart found a dead Sowerby's beaked whale on a Georgia beach; she photographed it and "collected its skull", and the article goes on to say

Almost nothing is known about the natural history of the Sowerby's beaked whale. They reach a length of approximately 18 feet long, travel in pods of up to 10 and presumably eat small fish and squid.

Presumably? Well, the first half-dozen google hits indicate that at least some of the stranded specimens from which almost all of our knowledge of this species comes were autopsied, and yes they do eat fish and squid; but any and all additional information is clearly useful. Come on Maggie, you've already cut the damn thing's head off, how much worse could it be to open up its stomach and catalogue the contents? (Well, OK, lots worse; but phenol will get that skin right off, and when it grows back it'll hardly stink at all.)

Nef inhibitors: I didn't think terribly highly of this idea when I was working on HIV and I still don't. A UCI team has used phage display to identify small molecules that can disrupt the interaction of the HIV protein nef with the host proteins p53, actin and p56^lck (read the full article here). Granted this is a valid proof-of-concept for small molecule nef inhibitors (and a means of screening for same), but that leaves a few small issues to be resolved:

• contrary to the press release assertion that it's nef's function, the interaction with these cellular ligands is poorly characterised
  
• disruption of the function of any of the host proteins in question is likely to be lethal (indeed, all the compounds identified were highly toxic)
  
• nef-deleted virus is infectious, can cause AIDS (albeit slowly) and can become more virulent, for instance by mutating coreceptor use (see this paper)
  

I don't want to sound too negative here though: I'm a big fan of antiretroviral drug development, because HIV is proving a tough target for vaccine initiatives and vaccines take a very long time to develop. I don't think the ultimate solution to HIV/AIDS is likely to be chemotherapy (for what it's worth, my money's on a combination of chemo and immunotherapy), but drug development can alleviate a tremendous amount of suffering and strongly curb the spread of the virus. A nef inhibitor could certainly slow down disease progression, adding many years to a patient's life, and would probably also reduce the risk of transmission.

Two new members of the blogroll today, both of them unusual.

Via Chris Mooney, the weblog of the American Bioethics Journal, blog.bioethics.net:

Why is a scholarly journal sponsoring a blog? We're no ordinary journal. The American Journal of Bioethics has from its inception been an experiment in broadening the reach of bioethics. From the day we first met with MIT Press to discuss their ideas for a new bioethics journal, we have been stretching our imaginations. Why not let writers read each other's commentary before it is published, so that a collection of commentaries on a major article reads like a conversation? Why not publish qualitative and even quantitative studies in a journal about bioethics? Why not use the online page of a journal to collect the core set of information about bioethics? Some of our ideas have been flops. We're betting that an "editors' blog" won't be.

Good points all, and I'm glad of an easy way to keep in touch with news and ideas in bioethics. (It's one of my frequent laments that I have a "doctor of philosophy" degree, and was not required to take even one philosophy of science or ethics class; all my learning in those fields has been self directed since I graduated.)

Via Preposterous Universe, 411blog (the service interface is here): a "mechanism whereby a symbiotic relationship between blogging and traditional forms of journalism can be deliberately cultivated". Another of the tirades to which I regularly subject longsuffering friends and relatives concerns the accuracy of science reporting. It seems that every time I see a mainstream media story about a subject I happen to know in some depth, the reporter gets important details wrong -- which does not inspire confidence in stories concerning the many subjects about which I know squat. This (411blog) is an attempt to connect reporters to bona fide experts who are self-selected for an interest in outreach and science communication and who are available on, essentially, a minute-by-minute basis via the web. I hope it succeeds; I'm going to nominate a bunch of folks from my blogroll.

This may be a bona fide breakthrough in virus detection: a Harvard group has reported specific detection of individual virus particles using silicon nanowires coupled to virus-specific antibodies. The article in Proc Natl Acad Sci is open-access, so anyone can read the whole thing and I don't have to feel bad about swiping their cartoon, which explains the principle at a glance. The authors use simultaneous electrical and light microscopy monitoring of individual nanowires to demonstrate that the changes in conductance are due to binding/unbinding of single virus particles. They show that the duration and magnitude of the conductance changes are characteristic of specific binding events, which are easily distinguished from diffusion events; together with antibody specificity this means that detection is highly selective and the false positive rate extremely low. Multiple viruses (well, at least two, but the system should scale readily) can be detected in parallel in a single sample. These features of the system offer a solution to the problem of antigenic variation that plagues other antibody-based detection methods, since multiple antigens can be targeted simultaneously and molecules other than antibodies, such as cellular virus receptors (e.g. CD4 for HIV), could also be used. The size of the detection units means that multiplex systems will not be physically unwieldy: a tiny array much like a computer chip could contain thousands of different detectors. Virus was detected with similar specificity and selectivity in purified and "unpurified" samples, but the latter just means allantoic fluid so it remains to be demonstrated that the method is robust enough to screen, say, body fluids directly. It's also not clear from the paper what sort of equipment is involved and whether it will adapt readily to fieldwork, though it's basically just a bunch of transistors so I don't imagine it's intrinsically fragile. The authors don't discuss virus quantitation, either, but that would seem to be a relatively straighforward issue (they show that event frequency is directly proportional to virus concentration in one figure).
The extreme sensitivity of the method offers hope of detection in the very early stages of infection. This alone could mean many years and much improved quality of life for millions of HIV patients, since it is much easier to maintain than to rebuild the CD4-positive cell population. Furthermore, very early detection may open a window onto a period of viral vulnerability in which medical intervention will be more effective than in later stages. In addition to detection, the method will be readily applicable to the study of viral binding kinetics and possibly to high-throughput screening for drug discovery. (via Eurekalert)

Ever notice how things that "everybody knows" are usually wrong? Here's another one (from here, concerning this paper):

It is an established fact that 98 percent of the DNA, or the code of life, is exactly the same between humans and chimpanzees. So the key to what it means to be human resides in that other 2 percent.

Argh. Actually, it's an established fact that this meme, or trope, or whatever you want to call it, is bollocks. Individual human genomes vary by about 0.08% at the single-nucleotide level, whereas human and chimpanzee genomes differ by about 1-1.5% at the same level. This is misleading, because single-nucleotide comparison means aligning comparable sequences base-by-base and counting the differences. In order to line up the two sequences in the first place, however, you have to introduce gaps into each sequence to allow for insertions and deletions. Like this:

actgccggctaac-----gtaccTgtcaactggcatgcatgcaagtacc
actgccggcGaacggtccgtacccgtcaac--gcatgAatgcaagtacc

In this made-up example, three bases out of fifty are different (6%) but the gaps account for a further 7 bases' worth of difference (14%). Do this with enough regions of each genome to get a representative sample and you can estimate the degree of sequence identity between the two genomes. Of the optimally-aligned sections of our genomes, we share about 98.5-99% with chimps, but taking the gaps into account produces a rather lower figure of about 95%, something Roy Britten showed in 2002.

What both figures overlook, and tend to obscure, is differences in the organization of large sections of the genetic information: duplications, inversions, recombinations between and within chromosomes, insertions of retroviral sequences, and so on. I wrote earlier about a method that allows us to measure such differences. Variation between individual humans on this scale seems to run at about 1.5% (cf. 0.08% at the nucleotide level); it will be interesting to see a ROMA-based comparison between humans and chimps. It is on this organisational scale that the real clues to the inscrutable Decree will be found.

I've been fooling around with the Bloglines blog feature, and considering turning it into a sidebar feed for this site. But then again, why not just make a second MT blog? In the meantime, I thought I'd recycle a few entries here.

Developmental patterning: this one's for PZM. Double-segment periodicity underlies 'odd' segment generation in centipedes

Apparently, centipedes have between 15 and 191 pairs of legs, and the number is always odd, and we don't know why. The paper to which this story refers indicates that segments are defined in pairs in the developing centipede embryo, and each segment develops a pair of legs. So why odd, and not even? The authors speculate that development of the forcipules ("poison claws", which are modified legs) reduces the resulting even number by one, resulting in an odd number. So the actual mystery mechanism in question is, what programs the forcipule development?

Bah. I just read the abstract, and the real story is how the co-ordinated expression of two different genes lays down a pattern of single-segment periodicity. That'll teach me to blog from the report not the paper.

Heh. Update to the update: the single segment periodicity is probably laid down in cycles that generate two segments each, and the generation of odd numbers of leg pairs may indeed be due to the extension of this process as far as the segments containing forcipule, genitals and so on. So the report was right, but (I found it) confusing. That'll teach me to trespass on Prof Myers' territory.

German science newsfeed. If you read German, this newsfeed, which I found by browsing science-related feeds at syndic8.com, is quite often well ahead of the English language feeds on my blogroll. For instance: yawning chimpanzees (German feed July 24, English feed July 26), the oncomouse patent (German feed July 6, English feed July 26) and the world's smallest fish (German feed July 7, English feed July 21).

Note that this works even for pretty feeble values of "read German". I can get the gist of most stories without help, but need translation help and/or a dictionary to actually understand what's going on. In fact, I originally added the feed to motivate me to pick up learning German again.

Colour perception is not innate, but acquired after birth.

The abstract is here. Monkeys raised for a year under monochromatic lights showed clear differences in their colour vision compared to those raised under normal conditions. I wonder how this relates to colour-related learning in humans with colour deficient vision (like, say, me).

Gene therapy reaches muscles throughout body, reverses muscular dystrophy. The paper will be in the August Nature Medicine, the abstract is available here.

Researchers at the Muscular Dystrophy Cooperative Research Center at the University of Washington School of Medicine have built an adeno-associated virus vector which specifically, and without eliciting an immune response, delivered an engineered dystrophin gene to every skeletal muscle, and the heart, of adult dystrophic mice. (Disruption of dystrophin production causes Duchenne muscular dystrophy in humans; without reading the paper, I assume the mouse is a knockout/similar model of the same disorder.) One injection of the viral vector caused a "dramatic improvement" in the animals' dystrophy.

Not only is this an important proof of principle for muscle-targeted gene therapy, it may be useful in other genetic disorders which do not even involve muscle tissue but simply require widespread expression of the therapeutic gene.

Something else that's good to see: the director of the MDCRC stressed that "the paper represents one discovery on the long path to any clinical applications in people [and] that there are a number of scientific challenges and regulatory requirements along the way, so any tests on humans are many years in the future" -- and the reporter included those quotes.

Chagas parasite invades genome (abstract here).

Trypanosoma cruzi kinetoplast DNA sequences end up in the host genome, opening up the possibility of some pretty freaky horizontal transfer of genetic information, plus influence on host evolution via mutation and creation of recombination hotspots. The article doesn't say "first time ever documented outside of retroviruses" so I guess other instances are known -- but I'd never heard of them.

ET first contact 'within 20 years'

Heh. Bullshit. Publicity seeking bullshit. (Don't get me wrong though, I *love* SETI and related goals/ideas; if this guy can bring in funding, more power to his bullshit generator.)

Surprising Degree Of Large-scale Variation In The Human Genome (the Science paper is here).

Researchers at Cold Spring Harbor Labs using ROMA (representational oligonucleotide microarray analysis) to investigate the differences between tumour and normal cells included a normal-normal control to establish lower limits of variability. What they found was that the genomes of normal individuals vary not just at the level of the individual nucleotide or even gene, but also on a much larger scale, with deletions and duplications from 100,000 b to 1 Mb (b = base, or more accurately base pair, a single "rung" on the familiar twisted rope ladder image of DNA).

What ROMA does (there's a good explanatory paper here) is to compare reduced-complexity representations of two genomes. The current average resolution is one probe every 35 kb. The authors say that 10-15 kb is feasible, but the more granular comparison may be more interesting, at least initially, because it shows the "big picture" -- like zooming out on a map. (There is some tradeoff, of course; earlier lower-resolution studies found far fewer polymorphisms.)

So, how big is 100 kb - 1 Mb? The entire genome is about 3000 Mb, and contains about 30,000 genes, so the "average gene" is about 100 kb. This is a bit misleading since a typical gene is a few hundred to several thousand bases of coding sequence, which may be spread out across hundreds of kb but is more usually contained within, say, a few tens of kb. So, 100-1000 kb is easily big enough to encompass a whole gene, or even quite a few entire genes. Indeed, the authors found variation in some 70 genes, including the gene which causes Cohen syndrome and genes known to be involved in neurodevelopment, leukaemia, drug resistance in breast cancer and body weight regulation.

The team compared twenty individual genomes and found 76 unique CNPs (copy number polymorphisms, the authors' name for the large deletions/duplications they are screening). The average CNP was 465 kb (median 222 kb) and individuals differed from each other by an average of 11 CNPs, so if the sample is representative (and the subjects were from a variety of geographic backgrounds) people differ from each other by around 4-5 million bases out of 3 billion, or 0.13-0.16%. The authors give multiple reasons to expect the observed CNPs to represent only a subset of the total, which they estimate to be 226 CNPs covering 44 Mb, or around 1.5%.

Comet Wild-2 is billions of years old and millions of miles away, travelling at 13000 miles an hour -- and we just took pictures of it, and grabbed a few handfuls of its dust. This gave me one of those "holy shit" moments that got me into science in the first place. (photo: nasa; you really have to go and see the high-res version)






I like to think I'm pretty straightforward and unsentimental about mortal remains, mine or anyone else's, but this guy has me beat by a mile.


I'd never heard of callimicos. They're cute. (Photo Credit: Edilio Nacimento Becerra / University Of Washington)












I love this kind of geekery, even if the songs do suck.


"New bug proves global warming"

"In all the other cases people say, 'Is this to do with global warming?' And we have to say we are not sure. But in this case we are sure."

Meh. First, prove that the London colonies are not metabolically different from the populations in warmer regions. Mutation is no less likely an explanation than global warming, and easier to falsify. (photo: bbc)




The obvious question arising from this is, do male and female humans have different levels of vasopressin in the orthologous brain region?


Hydrolagus matallanasi is a living fossil, like the coelacanth. Another scalp-tingly moment.


(AP Photo/Vale do Itajai University, Rafael de Alcantara Brandi)

Two Spanish researchers have shown (original here) that two leading journals routinely publish statistical errors:

The analysis revealed that at least one error appeared in 38 per cent of the Nature papers and 25 per cent of the British Medical Journal papers looked at. Furthermore, the study estimates that four per cent of results reported to be statistically "significant" may not be significant after all.

Yet again, the Spanish study is an example of someone actually doing something I thought of some time ago. (Fortunately for me, I'm usually only pleased when this happens, because I know perfectly well that I'll never do anything with the idea.) I am woefully ignorant of statistics, and probably have published overly simplistic analyses myself (though I am careful about claims of significance, and am confident that I've made no errors there). This sorry state is much more prevalent among biomed researchers than it ought to be, so I'm not suprised by the study's findings. Garcia-Berthou and Alcaraz also make another point upon which I've been known to wax shrewish:

As well as warning researchers and editors to be more careful with data, they also urge the publication of raw data online. "If we had that, we could check the results," Garc�a-Berthou says. "Some journals already publish supplements online, but it's rare, and I think it should become commonplace."

I think it should by now be viewed as low-rent not to make your raw data available online. There's no reason not to do it, unless you're hiding something; if the journal doesn't provide the option, the server space and bandwidth costs are well within reach of any research institution. I'm convinced that it will become a standard part of scientific publishing. (Obdisclosure: I haven't made any of my raw data available online, even though it was about the first thing I thought of when I came across the net, way back in 1993. I could never convince the higher-ups that it was a good idea. I'll start doing it as soon as I'm high enough on the food chain to insist on it, which I hope will be from the next paper onwards, paying for the hosting myself if need be.)

Researchers at NYU School of Medicine have found that Sindbis virus, a Togavirus that causes cold-like symptoms in humans, can systemically and specifically target tumour cells in mice. The press release is here, and the original paper in Nature Biotech is here. The virus enters mammalian cells by binding to the 67kDa high-affinity laminin receptor (LAMR), which makes it highly selective for tumour cells. Relative to healthy cells, the vast majority of tumour cells express greatly increased numbers of LAMR on their surfaces, and (again, unlike healthy cells) the majority of those receptors are unoccupied. (Normal LAMR function is involved in interaction with the extracellular matrix.)

Tseng and colleagues showed that Sindbis virus could infect tumours without infecting surrounding normal tissue and cause significant reduction in tumour mass (up to complete regression in some models) whether they induced the tumours subcutaneously or in the pancreas, lungs or peritoneum of immunocompromised mice using human cancer cells, or subcutaneously in immunocompetent mice using mouse cancer cells. This indicates that the results are not species specific and that a working immune system does not interfere with the anti-tumour activity despite repeated treatments with the virus. They also showed that the virus could infect and reduce spontaneous tumours in a cancer-prone mouse breed, decreasing the likelihood that the anti-tumour activity depended in some way on the manner in which the tumours were induced.

The virus was injected intraperitoneally or intravenously at as great a remove from the tumor sites as possible, which means that the virus targeted the tumours after being disseminated in the blood. This is great news, because it indicates that we can build a tumour-seeking virus missile that will find metastatic tumours no pathologist or surgeon could detect. It's also important to note that Sindbis is not a retrovirus (and so does not integrate its genome into the host cell's) and is highly lethal, so it kills virtually any cell it enters well before that cell could become a Sindbis-induced cancer itself. The virus used in this study was created in such a way that it cannot package itself into new particles after infecting a cell: it is replication incompetent, and cannot spread on its own through the patient's body. (Barring frankenviral recombination events, it only gives you a cold anyway.)

The images are from a different paper entirely (Zhang et al. J Virol vol. 76 pp. 11645-11658). Right, cryoelectron microscopy map of a partially deglycosylated Sindbis particle; left, surface topology model of same. Both pictures are to the same scale, the bar in the map represents 20 nm.

Today's Astronomy Picture of the Day took me back to my sci-fi¹ reading days: galaxy rise over Earth-beta, or something. Make sure you go look at the big version, which makes a great desktop.

¹ Yeah, yeah, "skiffy" blah blah whine snivel get over it already.

I've been meaning to write about this issue, but the sheer scope of it has caused me to procrastinate. Now, however, someone has done the work I should have (and then some), and things appear to be coming to a head. Angry Bear at The American Street links to this story from the Union of Concerned Scientists:

...more than 60 leading scientists—including Nobel laureates, leading medical experts, former federal agency directors and university chairs and presidents—issued a statement calling for regulatory and legislative action to restore scientific integrity to federal policymaking. According to the scientists, the Bush administration has, among other abuses, suppressed and distorted scientific analysis from federal agencies, and taken actions that have undermined the quality of scientific advisory panels.

As AB notes, the place to go for coverage of this issue is Chris Mooney's blog; his take on the statement is here. See also the "politics" category at Pharyngula for some bracingly bilious background on the Bush administration's hostility to science.

You can read the statement here, see a list of heavyweight signatories here, and if you're a scientist you can add your mark here (yes, I signed it). The statement itself is part of a wider campaign in which I urge everyone to get involved. One of the focal points of the campaign and the force behind the signed public statement is a report entitled Scientific Integrity in Policymaking: An Investigation into the Bush Administration's Misuse of Science; you can download the full report or executive summary as pdf files from here. You should read the whole thing, but here are the basic findings:

1. There is a well-established pattern of suppression and distortion of scientific findings by high-ranking Bush administration political appointees across numerous federal agencies.

2. There is strong documentation of a wideranging effort to manipulate the government’s scientific advisory system to prevent the appearance of advice that might run counter to the administration’s political agenda.

3. There is evidence that the administration often imposes restrictions on what government scientists can say or write about “sensitive” topics.

4. There is significant evidence that the scope and scale of the manipulation, suppression, and misrepresentation of science by the Bush administration is unprecedented.

Remember how the media kept calling Howard Dean "angry"? Listen: if you're not angry, you haven't been paying attention.

Like pretty much everyone, I've been using Tris-based buffers for nucleic acid electrophoresis since I started doing it. Turns out that the buffering capacity of the solution makes no real difference, and what you really want is a solution that doesn't carry so much current (and therefore doesn't generate as much heat; I've melted TAE/agarose gels before). I guess something was lost in translation between the interview and the article, because "carries a voltage" is meaningless to me. Also, I note that Kern and Brody have "filed for a provisional patent on the sodium boric acid solution" -- bwahahahaha! Good luck enforcing that. (In defence of the researchers, I suspect that beancounting shitbags at Johns Hopkins have made such idiocy mandatory.)

What's great about this is that everyone has been doing it the same way for thirty years, not bothering to think about improving the method since it worked well enough and, you know, that's the way everyone does it. Now these guys come along and deliver a smack-your-forehead moment to every molecular biologist in the world. *smacks self in forehead*

What's bad about this is that my one burning scientific ambition is to get a methods paper like this published, and I'm insanely envious. Why didn't I think of this? (Don't answer that.)

Porpidia flavocaerulescens, orange boulder lichen, photographed in Alaska by Steve and Sylvia Sharnoff, whose beautiful lichen sampler and gallery are taken from their book, Lichens of North America. (thanks to Anne Galloway for the link)

I never thought too much about the old adage that you can't fold a piece of paper in half more than 7 times; I tried with a couple of different pieces of paper, couldn't do it, and stopped there, except for a vague idea that I could do better with a much bigger piece of paper. Not Britney Gallivan, whose elbows you see there on a piece of paper folded 11 times (she's since managed 12). She derived expressions to describe the folding limits for one direction (L = (π.t/6)(2ⁿ + 4)(2ⁿ - 1), where L = length and t = thickness of the material and n is the number of folds) and alternating directions (roughly W = π.t.2^3(n-1)/2), then demonstrated the validity of her equations with gold foil and then with paper. Another approach is described here on Math Forum, or you can buy Ms Gallivan's booklet. I wish I'd had her chutzpah, not to mention her smarts, when I was in high school.

New Shrew: Texas Tech University professor Robert Baker has named Notiosorex cockrumi after his PhD supervisor. Baker discovered the shrew in 1966, but only recently confirmed that it is not the same species as N. crawfordi , which shares its home range in Arizona's Santa Rita mountains. Cute little sucker (but don't let that fool you: shrews are savage). Photo credit: Robert Baker, Arizona University.

Beleaguered Bongo Being Brought Back By Biologists: the last wild mountain bongo is thought to have died on Mt Kenya in 1994, but the species is not extinct thanks to hunter-turned-conservationist Don Hunt. Between 1970 and 1980, Hunt established a breeding program in the US that saw the captive population climb from the 20 he caught to around 400. On January 20, 18 bongo from the US joined 17 others at the Mt Kenya Game Ranch, where it is hoped that they will establish a semi-tame breeding pool with which to re-establish a wild population. If this story doesn't bring a lump to your throat, you're a serious hardass. Sniff. Photo credit: Mount Kenya Animal Orphanage.

Missing Monkey May Still Survive: no picture, sadly, as Miss Waldron's red colobus (Procolobus badius waldroni) is just too damn rare. Anthropologist Scott McGraw and colleagues declared it "probably extinct" in 2000, but shreds of evidence have rekindled hope that the species may survive in remote corners of the Ivory Coast. McGraw has a photograph, a skin and a tail, all of them collected in the last few years. Hunting and destruction of habitat have brought the Miss Waldron's to the brink; if they have in fact pushed it over, it will be the first recorded primate extinction in 200 years. Apart from being a shitty thing to do, that's a bad sign for the region because primates are extraordinarily adaptable, and the local ecology would have to be in really bad shape to have killed one off.

Several Species in Shark Decline: once the most commonly caught sharks in the region, oceanic whitetip and silky sharks have almost vanished from the Gulf of Mexico, according to biologists Julia K. Baum and Ransom A. Myers. Their study (Ecology Letters Feb 2004: vol. 7 pp. 135-145) compared 1950s and 1990s catch rates data and concluded that the whitetip, silky and mako shark populations in the Gulf of Mexico have declined by 99, 90 and 79 percent, respectively. The study has drawn extensive criticism; oddly enough, the critics cited work for the National Marine Fisheries Service and the Blue Water Fishermen's Association. The photo shows an oceanic whitetip (credit: Monterey Bay Aquarium).

Someone Otter Do Something: for reasons that remain unclear, the northern sea otter (Enhydra lutris) population of southwest Alaska has declined to the point where the United States Fish and Wildlife Service is listing it as "threatened", one step away from "endangered" under the Endangered Species Act. The Alaskan population was nearly eliminated by 1911, when an international treaty banned hunting; by the 1980's almost half of the world's northern sea otter population lived in southwest Alaska. Since then, the population has declined by somewhere between 50 and 70 percent. Photo credit: Friends of the Sea Otter; more info available from biologicaldiversity.org.

Insights into HIV-1 RNA dimerization: two RNA genomes are packaged in every infectious HIV particle, and they are joined by a specific mechanism at specific sites along the molecules. Researchers at NIST and CARB have shown that specific protonation of the dimerization initiation sequence loop residue A272 may be involved in dimer maturation. Read the abstract and, if you have access, get the PNAS preprint from here. If confirmed in vivo, this will be a novel role for protonation in RNA structure modulation.

New antioxidants: by chopping off its tail and substituting nitrogen into the two rings, Derek Pratt and colleages at Vanderbilt University have turned alpha-tocopherol (the most active in humans of 8 tocopherols that make up "vitamin E"; pictured at right) into a novel compound with about 90-fold greater antioxidant activity. Even if the new compound does not prove biologically useful, it will still probably find a home in the manufacture of oxidation sensitive products like plastics, rubber, lubricants and cosmetics. (image from Wikipedia.de)

Potential new antibiotics: chemists at the University of Illinois at Urbana-Champaign have demonstrated that a single enzyme is capable of processing the precursor LctA all the way to the lantibiotic lacticin 481 (abstract from Science vol. 303 pp. 679-81 here). Lantibiotics are small secreted microbicidal peptides that contain the modified amino acid lanthionine, and are particularly attractive as antibacterial agents because they inhibit cell wall synthesis and disrupt the cell membrane. This dual attack makes the development of resistance less likely than with agents that have a single target; for instance, the lantibiotic nisin has been used as a food preservative for more than 50 years in more than 40 countries without resistance related problems. Nisin is produced by certain strains of Lactococcus lactis, occurs naturally in a variety of cheeses and is classified GRAS (generally recognised as safe) by the USFDA. What's cool about this is that the biosynthesis of most antibiotics is so complex that it is virtually impossible to tweak it, but this system offers the possiblity of designer lantibiotics. By modifying LctA or offering other substrates to LctM, we may be able to generate a whole range of new lantibiotics. (The image, from The Microbial World, is just for decoration, and actually shows growth inhibition of Micrococcus luteus by Penicillium notatum.)

Killer bugs: but not from Outer Space. Bdellovibrio are bacterial predators which actively hunt and kill other bacteria. They are chemotactic, meaning that they can follow concentration gradients of substances likely to lead to prey, and have an impressive arsenal of lytic enzymes with which to enter the target cell and then, essentially, eat it from the inside. Researchers at the Max Planck Institute for Developmental Biology have sequenced the entire genome of Bdellovibrio bacteriovorus, and are looking forward to a smorgasbord of novel enzymatic activities. From the press release:

The researchers will attempt to identify the targets in the prey cell that have proven to be successful points of attack in this million-year-old prey-predator relationship. The lytic enzymes acting on cellular systems that are not targeted by conventional chemical antibiotics are thereby especially interesting.

Far reaching anti-microbial strategies aim at using Bdellovibrio as a "living antibiotic". This seems feasible, as Bdellovibrio is not capable of infecting eukaryotic cells, in particular mammalian cells. Moreover, it was shown in animal experiments that Bdellovibrio only has a weakly immunogenic surface, which does not produce serious life threatening reactions in test animals. These attributes, together with the facts that certain Bdellovibrio strains show a very narrow prey spectrum and are capable of penetrating the same tissues as many human pathogens, gives promise to the development of novel anti-microbial strategies.

The photomicrograph, which I swiped from here, shows B. bacteriovorus (I circled a couple) attacking Spirillum serpens (arrow). The white bar shows 1 millionth of a meter.

De-differentiation of adult cells is an alternative to the use of embryonic stem cells as a source of pluripotent cells that could be induced to form specific tissues in order to heal wounds, replace organs, and so on. Researchers at the Scripps Institute have used a library screening approach to look for small molecules (read: drugs) which can reverse muscle cell differentiation and allow re-differentiation along a bone cell lineage. While many questions remain, they have come up with a compound which they call "reversine" (pictured at left; pic from J. Am. Chem. Soc. vol. 126 pp. 410 -411) which appears to have the properties they are looking for.

Computer program speeds up x-ray data analysis:

Scientists are finding a computer program called Elves to be a nearly magical solution to the tedious and time-consuming task of determining the 3-D shape of proteins ... the first time anyone has reported a computer generating a protein structure by itself ... Elves decreases the time and training needed for researchers to interpret X-ray crystallographic data

The big deal here is that 3-D protein structures are the keys to solving an enormous range of biological puzzles, particularly those involving drug design, and this program has made the time from x-ray data to solved structure much shorter (good primers on x-ray crystallography here and here). That's good news not only in the immediate time-saving sense but also in the larger sense that it enables meta-analysis. By reducing analysis times from days/weeks to minutes, the new software will enable side-by-side analysis of, and comparisons between, much larger data sets. For instance,

Holton is taking a second look at X-ray diffraction data that other scientists have given up working on. He hopes to find out what characterizes the nine out of 10 data sets that fail to produce good structural data.

The image at right shows x-ray crystallographic data of considerable historical impact and interest: it was collected by Dr Rosalind Franklin in 1952 and from it was deduced the double-helical structure of DNA. (Incidentally, if you're interested in that famous story, rather than listen to that egregious prick Watson, read this excellent version told from the perspective of Linus Pauling.)

One of the best things about being a research scientist is that there is always good news to be had from somewhere in my own field or one close by. It always cheers me up to be reminded that the knowledge base is growing every day.


Closest look yet at HIV surface: a Florida State University team has used electron tomography to put together the most detailed images ever seen of the surface of HIV and SIV (S = "simian") particles. The pictures on the right show engineered SIV expressing high levels of the surface protein gp120 (indicated by arrows), from above (right) and from the side (far right). The propeller-like shape of the gp120 trimer can be clearly seen in the top-down view and again in the close-up below (also from above). The final picture shows a wild type HIV particle, showing the much lower density of gp120 (which came as a surprise; most researchers thought it would look like the SIV pictures). The white bar in the HIV picture is 100 nm, about 1/500th the thickness of a human hair; the same scale applies to the SIV pictures.




This is neat, but it isn't new: FRET (fluorescence resonance energy transfer) has been around for a while. The basic idea is to take two fluorescent molecules whose excitation and emission spectra overlap in such a way as to make it possible to excite one using the emission of the other. If you put energy in to the system at the lower excitation frequency and get back light at the higher emission frequency, it proves that the two molecules are in close contact. If you've attached one to protein A and one to protein B, wherever you see the higher frequency emission proteins A and B must be very close together (interacting); you can do this in a living cell to see when and where A and B interact. What's new in this study is that the two fluorophores have been attached to opposite ends of a single molecule which happens to fold differently in its active and inactive states. That's neat, because it allows you to monitor the activation state of the protein by monitoring the emission from the fluorophores. It's true that this is "the first probe of its kind that allows us to actually see in a living system where, when and how proteins are activated", but only because that's very narrowly defined, and the authors do not claim (as the article does) that it's an entirely new kind of probe. Bad reporter, no vodka.


Classic science; first, some background. Listeria monocytogenes is a most unpleasant organism, one of the most common causes of bacterial meningitis. Most bacteria, when taken up by specialized immune cells -- professional eaters-of-foreign-bodies called macrophages -- find themselves trapped in a small bubble of membrane called a phagosome, in which they are rapidly killed by acidification and digestive enzymes. Listeria, though, has found a way to break out of the phagosome, using a phospholipase called listeriolysin O. Macrophages are also professional antigen-presenting cells, meaning that they present foreign proteins to other cells of the immune system, enabling those cells to mount a specific response. Macrophages typically present proteins taken up from outside themselves (like bacterial proteins) to T-helper cells, which act to drive humoral (antibody-based) immunity. When what you want is to drive cellular immunity, macrophages can do that too, but usually the protein of interest has to be synthesized within the macrophage (like a viral protein). One of the long-standing problems in vaccinology has been how to get a foreign protein which is taken up from outside the cell (your vaccine) to be presented like a viral protein, as though it came from within the cell, so as to get a cellular immune response to back up the antibody response, which is often insufficient on its own.

So, what Lee's team has done is to make a vaccine formulation containing their vaccine target protein together with listeriolysin O. When liposomes containing both proteins are taken up by cells, the listeriolysin acts to release the vaccine protein into the cytosol of the cell, at which point it can enter the presentation pathway normally reserved for proteins made within the cell. In other words, Lee and co. have taken the method that Listeria uses to get safely out of the phagosome, and used it to get a vaccine protein out of the phagosome and into a cellular pathway that has until now been very difficult to access. Beautiful, elegant work. They showed, using a mouse viral meningitis model, that liposomes containing listeriolysin plus viral protein elicited a stronger cellular immune response than liposomes containing viral protein alone without antagonising the antibody response, and that this dual response was sufficient to provide sterile immunity against a challenge that killed half of the viral-protein-only group and 100% of unvaccinated controls. Inclusion of listeriolysin in vaccine formulations may provide a way to boost the levels of protection that can be obtained against agents that attack from within a cell, notably viral infections (SARS, HIV, Ebola, 'flu...) and cancer.

(You can read the whole paper for this one; because the study was reported in the first issue of a new journal (Molecular Pharmaceuticals) it's available online as a free sample).

I have pretty much given up on keeping my bookmarks organised on a day-to-day basis; I keep a few handy reference links that I use regularly (like Merriam-Webster online) and just use Google to find anything else I want from time to time (say, a currency or temperature scale converter). Other than that, I keep a toolbar folder into which I dump all the interesting links that come my way, and every now and then I sort those links into an organised set of folders. It's cleanup time again, so here are a couple of web goodies:

Winning greater influence for science. Daniel Yankelovich argues that there is an unspoken agreement between science and society which provides science with a "separation from involvement with goals, values, and institutions other than its own", and that

This "social contract" has allowed science to pursue long-term fundamental questions and to build slowly on the basis of its new knowledge. Science has been able to do this even in the context of a society such as ours, which in most domains is impatient, excessively pragmatic, and thinks only in the short term. But this same social contract is responsible for the widening disparity between the sophistication of our science and the relatively primitive state of our social and political relationships.

Most scientists of my acquaintance (and I am guilty of this too) treat the gulf between the public and our "ivory towers" the same way as everyone treats the weather: we complain, but we do nothing. Yankelovich at least suggests a model for dealing with the problem.

On a related note, Eugene Goodheart's essay Imperial Science takes on the "two cultures" view of CP Snow and his inheritors EO Wilson, Jared Diamond and Richard Dawkins. I'm probably a little more sympathetic to Wilson's side of things than Goodheart is, but the essay is a welcome thorn in the side of "sociobiology", that misbegotten offshoot of evolutionary biology which attempts to reduce human lives to formulae and ape-behaviours.

This could move biology forward in the same way (that is, to the same extent) that PCR did. Chemists at UC Berkely and Lawrence Berkeley National Laboratory have devised a novel method of measuring protein-protein interactions at cell membranes. Microscopic glass beads are coated with artificial membranes in which functional receptor molecules are embedded, and the behaviour of the beads in response to the presence of various binding partners in the surrounding solution is monitored. From the Nature article (vol 427, pp. 139 - 141):

The behaviour of a colloidal system is driven by the pair interaction potential between particles. In the case of membrane-derivatized silica beads, the pair potential is dominated by membrane–membrane interactions. Two-dimensional dispersions of lipid-membrane-derivatized silica beads exhibit colloidal phase transitions that are governed by details of these membrane surface interactions. The collective phase behaviour serves as a cooperative amplifier that produces a readily detectable response from a small number of molecular events on the membrane surface. Using direct optical imaging, we observe multiple near-equilibrium phases and find that protein binding to membrane-associated ligands at densities as low as 10^-4 monolayer can trigger a phase transition. Statistical analysis of bead pair distribution functions enables quantitative comparison among different membrane systems and reveals subtle, pre-transition effects.

That translates to an extremely rapid, high-throughput method for screening ligand-receptor interactions that is sensitive in the picomolar range and requires nothing more complex than a light microscope. Cool.

A heartening article from the Wildlife Conservation Society:

A recent census of the Virunga Volcanoes mountain gorilla population has found that the great apes have increased their numbers by 17 percent, according to conservation authorities in Uganda, Rwanda, the Democratic Republic of Congo (DRC), the Wildlife Conservation Society (WCS) and other groups. The results indicate a total of 380 gorillas, up from 324 individuals in 1989, the last time conditions were stable enough to conduct such a census. [...] Another population of 320 mountain gorillas exists in Uganda’s Bwindi Impenetrable National Park, which brings the current worldwide total of mountain gorillas to 700 individuals.

(Via PZ Myers' Pharyngula) Bruce Garrett, a software engineer at the Space Telescope Science Institute reports (with an update here) on the first casualty of Preznit Dimwit's determination boldly to go where, er, we've already been:

No more servicing missions to Hubble, as per the directive of the current head of NASA, Sean O'Keefe.

Hubble has six guidance gyros. But they fail at fairly regular and now predictable rates. Nearly every servicing mission to Hubble has replaced gyros as part of the work done. It needs three to do most of the science it now does, although there is a scheme in the works to do a greatly attenuated kind of science with two. We currently have four working gyros. Expectations were that we would almost certainly be down to two by the time the next servicing mission occurred, and possibly even down to one. So, figure, at around the time of what would have been the next servicing mission, Hubble will probably be no more, or soon, very soon, to expire.

Mainstream news (1, 2) also has the story.

That's the Little Ghost nebula, the remains of a dying star called NGC 6369. I swiped it from the images gallery at Hubble's homepage. Read, er, view 'em and weep. Deep space exploration just got deep-sixed for the time being.

From Scientific American:

Scientists report that they have developed a robot that can formulate hypotheses, design experiments to test them and analyze the results. What is more, it performs just as well as real grad students and spends less money.

OK, so it's not as bad as the entry title makes it sound. The real punchline here is not the bit about equalling grad student performance, which a monkey could do if my own grad school work is any indication; nor do I think that automatic methods of generating hypotheses and/or interpreting data have any real future, except in cases so simple that doing it with wetware is trivial anyway. The real kick is the potential for drastic reductions in monkeywork: one of these doohickeys could slave away 24/7 on the boring, repetitive tasks that make up the bulk of labwork. I hate that shit, and can't wait to dump it on someone (or somebot) else. Another thing about robots: they don't require initial training, and upgrades are presumably simpler than is the case with their vertebrate competitors; furthermore, a robot will not care if I am disagreeably sharp of temper and tongue¹. Given how hard it can be to get good hominid help (just ask my former employers!), I can see a real market for these things.

¹ I think of this as the uncharitable interpretation of my reluctance to suffer fools, gladly or otherwise; but then I would, wouldn't I?

This is about people I work with. It's a bit misleading in that the lab I work in (also here) is not actually part of the copper project and has separate funding, but the quote about mutual benefits is true and we do have good collaborations between the two groups. I have to wonder whether Ninian Blackburn (whom I have never met; he works on a different campus) came across as somewhat patronising to the interviewer, given the quote with which the piece ends.

Two from jwz:

Soviet exploration of Venus:

The Soviet exploration of Venus, from 1961 to 1984, is the largest effort ever undertaken to study another planet. The fundamentals of interplanetary spacecraft design and remote sensing were first realized in these attempts. Successful missions included 3 atmospheric probes, 10 landings, 4 orbiters, 11 flybys or impacts, and 2 balloon probes of the clouds.

And the best part? Pictures of the planet's surface!

[Update: it occurred to me that "Venus is pretty hot, isn't it?", so I looked it up. Yes, Venus is very hot: almost 500 °C. Not only that, but the surface pressure is 90 atmospheres, and the perpetual clouds are mostly sulphuric acid. The probe Venera-13 survived 127 minutes on the surface in 1982.]

PERV (porcine endogenous retrovirus) can be transmitted to human cells from the pig/human chimeric cells that form in pigs grown from embryos into which human stem cells have been injected. One of the aims of the research is (was) to create tissues that could be used in xenotransplantation. Some researchers would disagree with me:

...the question is how widespread and how many of these hybrid cells were found? If they are very rare - and we haven't found any in our experiments - then I don't think it is that important.

but I think this is the end of porcine xenotransplants.

In an aside to this post, Mark Liberman at Language Log links to a wonderful talk by Richard W Hamming on how to do significant research. This is a useful collection of observations for anyone who wants to go beyond the solid, plodding "good" to the really first-class. (Not, I hasten to add, lest this post come back to haunt me, that there's anything remotely wrong with "good". I have a long way to go to get even that far; and Hamming himself pretty much admits that, as a general rule, unless you are a towering Pauling-esque genius you can be happy or you can be significant.)

[updated, see below]

more...

Pericat agrees with Mike Täht that he, Mike, is not a lemming. I don't know Mike from a hole in the ground (though I'm sure he's a fine fellow), so what grabbed my interest was the article concerning lemming population cycles to which P also linked. The research paper on which the article is based is available here in pdf format. It's outside my area of research, so take this with an appropriately large grain of salt, but I am not convinced by the proposed theory. It rests on two ideas I find problematic:

1. plants producing lethal toxins (that they do not normally produce) in response to heavier-than-usual grazing. The mechanism of this toxin production must differentiate between regular grazing and "preferred food has all been eaten, so look out" grazing; if wound-induced toxin production were dose-responsive (more wounds, more toxin) that might work, but as far as I can tell the authors cite no actual examples of this occurring.

2. the idea that the primary reasons for a lack of toxin resistance development in the rodent population are the long (relative to generation time) periods between toxin production and immigration from susceptible genepools. The authors do not seem to explain how either of these is a defense against the fixation in the population of a mutation which provides toxin resistance and is not detrimental to reproductive fitness in the absence of toxin.

Finally, the authors state:

Evolved resistance will be delayed further if the toxins have a longer-term effect of interfering with breeding [...] This will reduce the probability of resistant residents breeding with each other

I don't buy that either. It seems to me that it only holds true if the resistance does not extend to the breeding interference, which does not seem likely; in fact, resistance to a toxin present in the primary food source during a food shortage seems likely to increase reproductive fitness.

How's that for a tangent?