give your brain a workout

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 peerreview, 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 Today, with ever increasing understanding of neurons, circuits and cognition, this concept has become outdated and any metaphysical account of free will is rightfully rejected.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.

Oprah and anti-vaccine propaganda

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.

New blog in town.

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.

Calling all bioinformaticians…

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.)

Changing views of science

I’m always a bit leery of, 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.
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.

What are these things?


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?

sic transit gloria mission statements…

nature.jpgNature 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 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
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 (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).

Nonsense, and pernicious nonsense at that.

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.

Is it ethical to encourage students to go to grad school in science?

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.