\tBut the paper had one glaring omission: the methods used to cool the crystals were not described.<\/p>\n
\tI was intrigued. No, truth be told, I was annoyed<\/em>. Because we were investigating the same protein and, try as we might, we hadn’t<\/em> 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<\/a> 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 It was largely superceded by cryo-cooling in the mid-1990’s, but the cooling can be tricky to get to work in some cases.<\/p>\n \t \tI 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.<\/p>\n \tBut 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<\/a> 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.<\/p>\n \tEven so, we didn’t do too badly. In fact we’ve done rather well (as I’ve mentioned before<\/a>) 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.<\/p>\n \tOther 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.<\/p>\n \tSo 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.<\/p>\n \tThe 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.<\/p>\n \tFrom 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<\/a> in the protein (though I don’t know<\/em> 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.<\/p>\n \tSo the next time you are reviewing a paper and forcing yourself to re-read the lifeless prose for the umpteenth time, please don’t<\/em> be tempted to fast-forward through the Materials and Methods. Give them all the attention they deserve. And then some. And then some more.<\/p>\n \tNow, where did I leave that piece of humble pie?<\/p>\n","protected":false},"excerpt":{"rendered":" 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 … Continue reading
\n![\"Frozen](\"http:\/\/farm4.static.flickr.com\/3382\/3471965974_b9669a2155_o.jpg\")
<\/a>
\nChill, baby. Cryo-cooled crystal in a nylon loop<\/em>
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