Reciprocal Space

Simon Singh is a brave man. He has announced that he is going to apply to appeal in his case with the British Chiropractic Association. He writes about the background to the case here.

Simultaneously, Sense About Science is launching its Keep the Libel Laws out of Science Campaign. It should be widely reported in the UK media today.

On the website you will find a statement written by Singh and a group of people including Tracey Brown (MD of Sense About Science), Edzard Ernst (Prof. of Complementary Medicine and Singh’s co-author on Trick or Treatment) and David Allen Green (lawyer, blogger and Nature Networker!) on the use of libel to silence scientific debate and calling for a parliamentary review of the libel laws. Around here it is by now, I hope, fairly obvious why this is an important issue.

The statement has already been signed by nearly 150 of the ‘top names’ in science, journalism, comedy, literature and the law including Lord Rees, Stephen Fry, Professor Richard Dawkins (stop twitching, Henry), Derren Brown, Professor Steve Jones and Dara O’Briain. (Interesting debate to be had there about scientific authority, but I digress!)

The statement has now gone live and you can sign to show your support. I’ve already done so.

Oh, and if you can, make sure to blog, twitter or otherwise Web2.0 about this. Please send the link to your friends and ask them to sign too.

The statement has already been sent to the Prime Minister, the Department of Culture, Media and Sport and the Department of Justice and it will be sent again — and again — with every 1000 additional signatures that are received until there is a commitment and a timetable from the parties for the necessary legislation.

This will probably be a long and tortuous journey.

My most recent post, “Respect my Authority!”, which was an attempt to explore the origin of scientific authority, has been removed by Nature Network because their legal advice deemed it to contain some dubious assertions.

The matter was handled with great care in phone conversations with Corie and an email from Timo. I am grateful to them for the consideration they have shown. I have no doubt this was a tortuous decision. I’m relatively new to this game and have no desire to be sued or to cause serious problems for NN. So I decided to take the legal advice on trust and agreed to the removal of the post.

Ironically, the wider intent of the piece was to assert that scientific authority derives largely from the culture of open and robust debate that exists within the scientific community. But that culture is under threat, at least when it seeks to engage with the wider society. That was already clear from what I heard at the Skeptics in the Pub meeting about the Simon Singh case, which has brought to light the powerful reach of English libel law. Following my account of the meeting, Maxine set up a forum topic, Using the law to stifle scientific debate, to foster more discussion. I urge you to take a look and to peruse some of the links to recent newspaper articles on this topic.

It is certainly feels odd that my post is the first on NN to be stifled by this law. I’m going to have to think about what this means for future blogging activity. I don’t yet know exactly what to say – or how to measure my words in future. This development seems to introduce a level of self-censorship that I had not been fully aware of before. If I can find a positive note, it will make us rely even more heavily that we already do on solid evidence.

And I am going to offer enthusiastic moral and material support to the campaign to reform English libel laws.

There was a very nice piece in yesterday’s Nature by Ananyo Bhattacharya (a former PhD student of mine who now works for the journal). Ananyo discusses the current structural ‘wish list’ with some of the world’s most ambitious protein crystallographers.

Perhaps I’m a little biased but I think it’s beautifully written. Even if you have only a passing interest in the structures of large biological molecules, I recommend you have a look.

When I was a little boy I remember that my mother would sometimes extract a dull metal implement from the dark recess of a rarely used cupboard and clamp it to the kitchen table. Turning the handle she would feed the device with cubes of beef and it would spew mince onto a cold white plate.

This is what my brain feels like.

I have read fourteen grant applications in the past few days in preparation for an upcoming funding committee meeting. Each of them was densely written, crammed onto the page, and just as densely argued. My brain has turned to mush. Its shredded cortex has left me few resources with which to fashion a blog post but fortunately I have some material that I prepared earlier.

These days it is almost de rigeur for writers of blogs to plug themselves into that other piece of Web2.0 wizardly, the podcast. There have been several recent examples from among our number: stand up Katherine, Brian, Henry and Eva). And it was hearing Jenny Rohn on the Guardian Science Weekly podcast that originally got me into all this. So you know who to blame.

Until recently I had never ventured into audiospace but, like buses, two opportunities have just come along. The first is the inaugural Lablit podcast where, as guest-chair, I led the discussion on Jenny’s highly engaging first novel, Experimental Heart. The recording, nicely edited by Richard, gives a great flavour of the discourse.

And then, thanks to the good offices of NN denizen Sara Fletcher, I was interviewed by Naked Scientist Meera Senthilingam for the Diamond Light Source podcast. Diamond is the UK’s sparkly new synchrotron, a giant X-ray generating doughnut that nestles in the Oxfordshire countryside. Having made use of the facility last December, I got the chance to talk about our work on the foot-and-mouth disease virus protease. Have a listen, if you like—the interview starts at about 12m 30s in and lasts about 7 minutes. If you’ve seen the video, you may recognise the story. T-shirts will be available soon.

I cannot properly judge what it is like but I was at least reasonably impressed by my lack of ums and aahs!

I should have done this a long time ago but I was too proud. I think I need to review.

In 2002 Dan Carter published a paper in BBRC describing the crystal structure of the protein, human serum albumin, complexed with hemin. It was a very interesting piece of work, not least because it was the first determination of an albumin structure from crystals that had been cryo-cooled all the way down to -173°C. This was an important advance because the cryo-cooling reduces the awful damage that X-rays mete out to proteins as they rip through the crystals in the experiments used to determine the protein structure. Basically, if you can freeze your crystals, you can get better data.

But the paper had one glaring omission: the methods used to cool the crystals were not described.

I was intrigued. No, truth be told, I was annoyed. Because we were investigating the same protein and, try as we might, we hadn’t got cryo-cooling to work. Instead, we sealed our precious crystals in thin-walled glass capillary tubes at room temperature, using a technique first developed by the ingenious and irrepressably bohemian JD Bernal in the 1930’s. The capillary method works well as long as your crystals are big enough (fortunately, ours usually were) but tends to limit the resolution of the X-ray data. It was largely superceded by cryo-cooling in the mid-1990’s, but the cooling can be tricky to get to work in some cases.

 

Chill, baby. Cryo-cooled crystal in a nylon loop
 

I wrote to the editor to complain about the omission from Carter’s paper and got short shrift. BBRC was a rapid publication journal, he shrugged, and the referees must have missed it. I should take the matter up with Carter.

But I didn’t. I hesitated. And that hesitation turned into a pause that lasted years. We had tried to get the cryo-cooling method to work ourselves but without success. Albumin is a notoriously flexible protein and the crystals can be very fragile. They weren’t easy to grow in the first place and we were reluctant to keep ruining them in failed cooling attempts; the students needed to get their PhDs after all, and the postdocs their papers. Clearly we should have tried harder but we surmised that the crystals were just too delicate to withstand the shock of rapid cooling. I didn’t want to admit our lack of progress to Carter, who was our main competitor in the field, so we soldiered on with our capillaries.

Even so, we didn’t do too badly. In fact we’ve done rather well (as I’ve mentioned before) and published about 20 papers on the structure of albumin and the various molecules that bind to the protein on its circuitous journeys through the bloodstream. It’s been a very rich seam but we’ve mined heavily and are now moving on.

Other labs are now getting in on the act and I would like to think that–in part–they have been stimulated by our work. So when I was asked recently to put together a review article on the crystallographic analysis of albumin, I decided to add some further impetus by including a lengthy section summarising in detail the techniques that we and others have used to grow albumin crystals and to handle them in X-ray diffraction experiments. This brought me back to the vexed question of cryo-cooling. More recently, a couple of new groups have started to apply this method to albumin, but not all have published details. A lab in China had reported a structure determined from cryo-cooled crystals of albumin but, like Carter, omitted their methods.

So back in February I emailed the Chinese group. And because it was only fair, I gulped down my pride and finally contacted Carter to ask about his 2002 paper.

The Chinese group leader replied quickly and candidly. They had been reluctant to include the method because it was unreliable. That was no great surprise to me, given what I knew about the delicacy of albumin crystals. But, I argued, that very unreliability was a reason to publish, not to withhold the methodology. Reporting it would give someone else the chance to grab the baton and run with it. We discussed back and forth in a few cordial email exchanges. I still don’t know what their methods are, but they have at least agreed to report them in detail in their next paper. I’ll be sure to watch out for it.

From Carter, I’ve heard nothing. I waited a couple of weeks and sent a polite reminder. Still nothing. My guess is that he won’t reply and than his silence may be due to his commercial interests in the protein (though I don’t know for sure – just in case he’s litigious!). I’ve no problem with people wanting to develop their results into valuable new technologies, but if they want to publish papers and play the science game, then I want them to play straight. No funny business.

So the next time you are reviewing a paper and forcing yourself to re-read the lifeless prose for the umpteenth time, please don’t be tempted to fast-forward through the Materials and Methods. Give them all the attention they deserve. And then some. And then some more.

Now, where did I leave that piece of humble pie?

Today I finally made it to the Darwin Big Idea Exhibition at the Natural History Museum in London. I had been concerned that our almost legendary lack of familial organization was going to prevent us from seeing it (Matt caught it back in January). But late last week I summoned the wherewithal to log on and book tickets, just managing to sneak in a visit before the show closes.

The school Easter holidays are still in full swing, so we had to bump our way through packed corridors to get to the entrance. With a cursory glance at our timed ticket (twenty-five quid, thankyouverymuch), the attendant ushered us into the dimly lit exhibition rooms.

The very first item on display (after the ‘No photography’ sign) was a brace of mockingbirds—laid out on their backs—that had been shot and tagged by Darwin on two adjacent Galápagos islands. The perceptible differences in beaks and plumage between these birds, rather than the more celebrated finches (which he didn’t cotton on to until much later), helped to stimulate Darwin’s thoughts on variation. This was the real deal – here were specimens collected by the man himself.

And there were more treats in store. A letter from Captain Fitzroy to Beaufort, giving thanks for his lucky choice of Darwin as a sailing companion. One from Darwin, offering observations on his adjustment to life aboard the Beagle. For the record, Fitzroy’s hand-writing was much neater.

Further on there was a real coup – Darwin’s notebook in which appears the famous diagram of the tree of life, evidently his first conceptualization of descent with modification:

I think, therefore I am an evolutionary biologist.

I read through the card posted to the side of the display case to glean the background to this famous document and at the bottom spotted an important word. It was very telling, shocking even. It said:

Continue reading →

As a crystallographer from County Antrim in Northern Ireland, it should come as no surprise that I am much taken by the Giants’ Causeway, an impressive basalt rock formation on the north coast that boasts some of the largest crystals in the world.

Hexaogal crystals in Co. Antrim – each column is about 60 cm across.

 
Even though London is now my home, I have often visited and made sure that my children have become familiar with the area. When asked his opinion of the Causeway, Samuel Johnson is reputed to have opined, “Worth seeing, yes, but not worth going to see.” But the man was a fool, as far as I can make out. I may be partial but it’s amazing.

Care: Slippery when wet.

 
So I was tickled a deep shade of pink the other night when watching Guillermo del Toro’s fabulous Hellboy II: The Golden Army. Because the plotline sent ‘Red’ and his merry band all the way from Manhattan (well-known orifice of the underworld) to the familiar green coastline of North Antrim, on a quest to find said Golden Army.

You can tell it’s Northern Ireland from the look of the sky. (From the IMDB)

 
Would you believe it, the army was right there, hidden in a monstrous cavern beneath the cliffs. And so ensued the elaborate, violent and inevitable final battle of the film – great stuff! All the more enjoyable because a little bit of movie-magic touched a place near to where I was born.

Attending the spring meeting of the Society for General Microbiology in sunny Harrogate earlier this week I had the chance to hear Stanley Prusiner deliver the SGM Prize Lecture on “Prion biology and diseases”. Not bad as talks go, though he would never win prizes for the design of his slides.

Prusiner won the Nobel Prize for Physiology or Medicine back in 1997 for his work to establish the prion hypothesis. It was ground-breaking stuff: self-replicating proteins that caused neurological disease. He had to fight his way through plenty of adverse, not to say derisive, opinion to get published and funded. In his talk he swept though this early work quite quickly to bring us up to date on more recent progress. Some of the assays they do are staggeringly long, involving as they do monitoring the disease symptoms in infected mice for more than 600 days. And I thought crystallography was slow!

Prusiner (left) receives his prize from the King of Sweden

But the most engaging segment came at the end when he allowed himself to be philosophical about winning his Nobel. For the benefit of the younger members of the audience he offered a few thoughts on what it takes to be a winner (a subject I have touched on before). His contention is that it is better to be lucky than brilliant, since luck has a big role to play in bringing your work to prominence.

He cited his own work on prions as a case in point. He had started out thinking that the disease-causing agent was some kind of tough but slow virus; if it had been, the work would have been interesting but hardly earth-shattering. The prion proteins could have been a bit less abundant in brain tissue; if so, they would have been undetectable using the techniques available to Prusiner at the time. He might have made the discovery 10 years earlier; if he had, it would have been too early to pursue the topic in any depth until molecular biology techniques were better developed. He might have been scooped by another scientist working on the same thing (something that happens all too commonly); if so, that would have been that.

And then in the early ‘90s BSE and vCJD erupted dramatically in the UK, bringing prion diseases to massive but unwelcome prominence, and Prusiner’s work very much into the public eye. The rest, as they say, is mystery history.

So there’s hope for all of us. Well, it may be too late for me (or Jenny?). But before all you young’uns start relaxing and waiting for great good fortune to roll up, let me mention that Robin Weiss, who presented Prusiner with his SGM prize, recalled in his remarks Pasteur’s maxim: chance favours the prepared mind.

Now get back to work!