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Guest post by Heather Cassell
One of the great joys of being in the lab is being in charge of your own experiments, from designing what you want to study to the interpretation of the results. Having responsibility for your work from conception to completion is challenging and ultimately rewarding.
The first step in designing your experiment is to find out what you want to know. That sounds simple and obvious, but it really is key to providing focus when planning your work. You must consider why you are doing this experiment, what it could show, how it fits with your other work, and, importantly, will you be able to interpret the results in a meaningful way, providing answers you can build on?
Inspiration for your experiments can come from diverse sources, beyond the traditional scientific lectures or academic literature, a conversation with a current or former colleague can be all it takes. But whatever the source of the idea, it is always a good idea to check if anyone else has beaten you to it by consulting the literature. Not that repeating existing work is a bad idea – you can see if existing studies are reproducible and if so, embellish or add to the data. Or you can change the design of your experiment to fit with your own previous studies, and may find something new.
Once you know what you want to do, it’s time to plan the details: what samples do you have, how many repeats do you need to make your results significant, and – more importantly – how are you going to tell if your experiment has worked properly? This is where planning the correct controls can make a big difference: I learned the hard way that it is good to include both positive and negative controls for every experiment. I wasted a lot of time trying to get an experiment to work, changing conditions one-by-one, when it was really a denatured enzyme stopping the reaction. A positive control means you always get a result, which is much better than no result. This is especially true when you are doing PCR; there are few sadder sights for a biochemist then a picture of a gel with just a ladder.
But I’ve also had it the other way – where I happily reported what seemed like a great result, only to find out that it was an artefact of the experimental design and my results became insignificant when I included different controls. Proper planning could have prevented that problem.
But that’s it! Once you have your experiment planned, designed and justified to the powers that be, you can return to your natural home in the lab and try it out. Ideally, things will run smoothly and every experiment will go without a hitch. You may encounter problems – but fear not! Every experimental error is an opportunity to learn, get back to the drawing board, then return, freshly inspired, to the bench.
Guest post by Rowena Fletcher-Wood
If necessity is the mother of invention, discovery is more than fuelled by fashion. After the 1985 groundbreaking discovery of the buckminsterfullerene, the ground for stable carbon allotropes with interesting shapes and properties was just that – broken. In 1990, Richard Smalley postulated the existence of carbon nanotubes as long, extended hexagon-based versions of C60, or ’buckytubes’. Carbon dirt had never looked so good before, and the mucking about began.
Graphene flakes were first isolated at Manchester University by Andre Geim and Konstantin Novoselov in 2003, when they noticed the technique surface scientists were using to clean graphite samples – peeling off the contaminated upper layer using pieces of sellotape. The pieces of sellotape went in the bin, but Geim and Novoselov fished them out again – and started painstakingly peeling off thinner and thinner layers until they made 1 atom thick graphene. They were awarded the Nobel prize for physics in 2010.
Sumio Iijima, who is often credited with the discovery of carbon nanotubes, attributes his discovery to serendipity. He had been studying diamond-like carbon, an amorphous diamond phase, using the new arc discharge method developed by Donald Huffman and Wolfgang Krätschmer in 1990. The rod-like carbon dirt surrounding his diamonds captured his attention: carbon tubes 3-30nm in diameter. Later, attempts to introduce transition metals to these tubes would lead him to create single-walled carbon nanotubes, a finding submitted to Nature for publication on 23 April 1993, one month before the US team headed by Bethume submitted exactly the same accidental result.
But whilst Iijima may claim that ’discovery was not simply coincidence – it was the power of serendipity’, it would be fairer to say that carbon nanotubes were rediscovered. Carbon-based filaments were recorded as long ago as 1889 by Robert Bacon when decomposing methane. But back in 1889, there was no such thing as a transmission electron microscope (TEM), and so no nanoscale imaging to view and characterise these filaments. The first TEM appeared in 1939, and the first TEM images of tubular nanoscale carbon tubes was published in 1952 by L. V. Radushkevich and V. M. Lukyanovich – but in a Russian journal, and in Russian. Published during the cold war, this paper went largely unread in the west. Although single-walled carbon nanotubes were first announced in the 1993 issue of Nature, TEM images from Oberlin et al. in 1976 indicate that successful synthesis had already been achieved.
And the carbon fever has not died down. In 2013, carbon ’sea urchins’ were accidentally prepared by researchers at Queen Mary and Kent Universities, growing on the surface of their carbon nanotube equipment. Intentionally roughening the surface accelerated the synthesis of these spiky iron-filled carbon balls with unusual magnetic properties. Although exciting applications such as permanent magnets, cancer therapy and batteries that charge from waste heat have been proposed, it seems likely that, like other carbon nanomaterials, new discoveries will outpace implementation: cheap and efficient production of carbon nanomaterials of a high enough quality has not yet been achieved.
It is only when nanomaterials are of a very high quality that the awesome properties may be observed, such as very high conductivity, luminescence or the ability of graphene sheets to filter hydrogen from the atmosphere for generating electricity. When we speak of the 1991 discovery of carbon nanotubes, it is perhaps the discovery of their properties and future potential to which we refer, rather than simply the creation of a new carbon allotrope. Carbon nanotubes have the highest pressure resistance of any known material, withstanding pressures of up to 63Gpa. They are ultra absorbant, heat-resistant, and at very high temperatures carbon nanotubes shimmer, loose their shape and become almost invisible, just like their origins.
If you are interested in hearing more about nanomaterials, structures and unusual properties, the Environmental Chemistry Interest Group of the Royal Society of Chemistry are holding an event in London on 24 June.
Last week, we heard from Derek Lowe about the evocative smells associated with working in the lab. Inspired by Derek’s olfactory adventures, the Chemistry World and Education in Chemistry teams shared their own experiences.
This week, we hear from our regular guest bloggers Tom Branson, Heather Cassell, JessTheChemist and Rowena Fletcher-Wood about their own smelly memories, along with a few more from the #labsmells hashtag.
— Astril Tifs (@firstilast) February 14, 2015
Chemistry has ruined me for marzipan.
Not just marzipan, of course, almonds, almond flavouring, even apricots. If you waft a piece of almond cake under my nose unexpectedly, I will automatically give an sudden and violent sniff, and recoil physically. I can’t help it, it’s an instinct, and that smell is the smell of hydrogen cyanide.
Early on in my chemistry career, when I was still in school, we conducted an electrolysis of brine, rapidly evolving chlorine gas into the lap until I felt woozy and had to go outside. It wasn’t the only time I nearly gassed myself. There were more than a few faulty fume hoods, or ones we had simply forgotten to switch on, and the ammonia gas cylinder that popped its collection flask and started dumping poisonous gas into the lab. We used cyanide during my undergraduate in solutions to create colour chemistry. It was terrifying – the only way you knew it was going wrong was if you smelt the cyanide, and the difference between first smelling it and the toxic effects of it is not much. I bent over the solution, sniffing frantically so as not to miss the first signs. I was so paranoid I was imagining smelling it, confused between reality and expectation. But the smell was never as strong as in marzipan – ergo marzipan must be fatally toxic.
I’ve been doing full time chemistry for eight years now. I think like a chemist. The logic circuits in my brain just can’t accept that marzipan is a safe food. It’s toxic. Step AWAY from the marzipan.
Within the lab there are many smells that I enjoy, such as yeast and agar which remind me of growing E. coli, a bacterium I also like the smell of. I like the smell of acetone and isopropanol used in small amounts in reactions and for cleaning glassware. Dilute acetic acid as it reminds me of the vinegar on fish and chips. Another bacterium, actinomycetes, release geosmin as they are growing – that compound gives soil the particularly earthy smell, especially after a heavy summer shower.
But there are also lab smells I really don’t enjoy, for example the beta-mercaptoethanol that I use to set sodium dodecyl sulfate (SDS)-gels for electrophoresis. I now have its use down to a fine art to reduce the exposure time: open the bottle one-handed, pipette the amount needed with the other hand, close the bottle again a quickly as possible whilst adding the liquid to the gel solution. Only once the bottle is closed do I gently mix and pouring the gel mix into the glass plates. Then there’s the smell of chlorine, released from a too concentrated Virkon solution. It’s bad enough when used in solution to clean glassware after growing bacteria, but it is definitely worse if it is in an aspirator trap. As soon as you turn the pump on it fills the room with a chlorine smell that can strip the hairs from your nose, and will linger in your clothes and hair for ages.
I’m certain that my aversion to the smell of ethanol stems from one overindulgent night. Not one spent sniffing chemicals in the lab but rather one spent drinking chemicals in the pub. Vodka shots used to be my bread and butter, but no longer. My senses are now unable to disassociate the highly alcoholic drink from its active ingredient. Since that fateful night I now grimace every time I have to disinfect a biosafety cabinet. A sharp whiff of ethanol and my mind leaps back to that memory, or at least the after-effects. However, one good thing that has come from my dislike of pure ethanol is a new fondness for gin and tonic.
— Lee Vousden (@Lee_Vousden) February 13, 2015
As a PhD student, I frequently worked with elemental fluorine, the flammable and highly toxic halogen gas. Fluorine can be smelled at around nine parts per billion, which is a similar odour detection threshold to that of hydrogen sulfide. It is hard to describe the smell of fluorine, but it is unpleasant and vaguely smells like a mixture of ozone and chlorine. Although the smell is remarkably offensive, its pungent odour does mean that the smallest leak in your reaction set-up can be identified very quickly and fixed. So while fluorine was a smelly, unpleasant chemical to work with, its smell was extremely useful from a safety perspective.
I love the #labsmells of Cp* in the morning. Smells like – chemistry.
— John Arnold (@pbn2au) February 13, 2015
In this month’s Chemistry World, Derek Lowe writes about the memorable smells associated with a career in chemistry, including the fragrantly fruity funk of esters and the suspicious seaside stench of amines.
Inspired by Derek’s olfactory adventures, I asked a few of the Chemistry World and Education in Chemistry team to recount their own experiences of lab smells, and opened it up to the twittersphere under the hashtag #labsmells:
— Alex Sinclair (@Alex_Sinc) February 11, 2015
Philip Robinson, Deputy Editor, Chemistry World
As a PhD student in the ‘dry’ half of a biochemical NMR group, most lab smells were associated with a sense of relief that I was at last free of the chaotic caprice of real chemistry. But on occasional trips down the corridor to see how the other half lived I’d often encounter the bold odour of the yeast cultures that were busily building our proteins.
That heavy, dense aroma, fusty and overripe evokes equal parts revulsion and pleasure and sends me further back, to boyhood, sat in the back of the family car holding my breath to avoid the scent as we drove past Edinburgh’s reeking breweries. But those many years later, my tastes matured, I’d often stand outside the department when the wind blew just right, looking up at the darkening blue of the evening sky and drawing in deep lungfuls of that delicious air. Opening a jar of vegemite brings it all back these days.
@ChemistryWorld H2S. Smelly and deadly.
— Rams (@ramadam09) February 11, 2015
— Sarah Zingales (@SKZingales) February 11, 2015
Phillip Broadwith, Business Editor, Chemistry World
One of my most memorable lab aromas is when Paul (Docherty) was using hexanoic acid in the lab. Also known as caproic acid, from capra, the latin name for goats, because that’s exactly what it smells like. In fact, in the listing for caproic acid in The Merck Index, under ‘properties’, you’ll find the sentence ‘Oily liquid, bp 205ºC. Characteristic goat-like odor’.
It’s one of a family of alkyl acids that all have interesting odours, varying as the chain length increases from smelling of pain (formic) through vinegar (acetic), cheese (propanoic), vomit (butanoic) and animal faeces (pentanoic), before the molecules become less volatile as they get heavier.
Fortunately, I didn’t need to raid the chemical store to find out about these smells, because Dylan Stiles (former CW columnist) wrote a brilliant post about it on his (now defunct) Tenderbutton blog. (the archived blog can be accessed using the username tender, password button)
— Louis Redux (@LouisRedux) February 11, 2015
— Fer (@gomobel) February 11, 2015
Katrina Krämer, Graduate trainee, Chemistry World
In the last half year of my PhD project I started making phosphine ligands using diphenylphosphine as the nucleophile. I got to know phosphines (tertiary ones that is) as tame, usually colour- and odourless powders. Secondary phosphines, however, are a completely different story.
I agree that there are many nasty smells in the lab, but at least I can place those smells – amines smell like rotten fish, thiols like garlic or old cheese. Describing the smell of HPPh2, however, is difficult: somehow sickly sweet, with some rotten carcass thrown into the mixture, a strong metallic aftertaste and extremely potent – I don’t think I ever smelled anything even remotely resembling this, and I don’t think I want to ever again.
After getting a bunch of looks that could kill from my labmates after rotavapping a flask with residual HPPh2 on the bench (we didn’t have a rotavap in a fumehood), I set up a massive bleach bath next to my fumehood, in which I immediately immersed all glassware that had come into contact with the nasty phosphine. But even through the bleach (since diphenylphosphine is stable enough to survive some days of bleaching) I could still smell the phosphine when I opened the bucket. From then on, I started doing all glassware washing inside my fumehood rather than in the sink.
When my supervisor suggested I should try different phosphines, in particular asymmetric ones like HP(Ph)Me, I vehemently declined – having done my homework, I knew that other secondary phosphines were another step down the ladder of evil odours. After sending him some further reading on the topic, my supervisor agreed, so luckily HPPh2 was the nastiest smell I ever encountered.
— lauren tedaldi (@LaurenTedaldi) February 11, 2015
@ChemistryWorld ..the smell of benzaldehide semilar to almond juice smell..it always remindes me of summer smell♥★
— salwa (@salwayussef) February 11, 2015
Paul MacLellan, Deputy Editor, Education in Chemistry
I had the pleasure of doing a PhD in organo-sulfur chemistry. By far the most onerous compound I had to make was a small thioester substrate. It wasn’t the worst-smelling compound I dealt with – indeed, the next step in the synthesis involved reducing it to a terrifyingly metallic-smelling thiol. But the reduction could be done on a small scale, whereas I had to make several grams of the thioester at a time.
Over a couple of weeks I built up something of a reputation in the surrounding labs (it didn’t help that this was early on in my lab career and I wasn’t perhaps as rigorous in containing the odours as I came to be soon after). Some people commented on the stench of the thioester being reminiscent (in the worst way) of bacon. Others identified marijuana. But to me, the smell inexplicably conjured memories of camping as a kid.
This remained a mystery to me for a year or so until a friend of mine visited my lab. While I was showing her around she picked up a faint background odour. A long-suffering Londoner, she identified it immediately. ‘Fox piss.’ Perhaps my parents should have pitched our tent more carefully.
— FX Coudert (@fxcoudert) February 11, 2015
— Preston MacDougall (@ChemicalEyeGuy) February 11, 2015
Matt Gunther, Science Correspondent, Chemistry World
The smell of cyanoacrylate, commonly known as superglue, is a laboratory smell that will forever haunt me. As part of my research I was tasked with imaging invisible organic matter on a steel surface. Inspired by CSI, I decided to form acrylate vapour in an enclosed chamber – the vapour reacts with the organic to produce a white residue.
One day, I opened the chamber and the smell hit me. Before I had to time to react to the smell, I realised I couldn’t see. Turns out I’d superglued my eyes shut.
— Preston MacDougall (@ChemicalEyeGuy) February 11, 2015
— Dave Belyea (@ve5rb) February 11, 2015
Guest post from Tom Branson
Last month I took a look back at the journal covers from Chemical Science in 2014 and asked the authors why they made these startling images. To follow on from these enlightening insights, I delved a little deeper and sought to find an answer to the ultimate question, which is of course: what makes a good journal cover?
Scientific and public audiences
To answer this question you first have to decide who the target audience(s) are and what you want to show them. Most of the authors I spoke to agreed that the image should be accessible to the general public. Julia Weinstein from the University of Sheffield, UK, whose cover was out last March, expressed the difficulty in also keeping the specialists happy. An image needs to have ‘general importance (for general public), and some fine details which will be of interest to professionals. It is a virtually impossible task!’ she said. However, how many members of the general public ever actually see these masterpieces is a question for another time.
Ultimately, the artwork must be visually appealing. If it does not encourage readers to look further into the paper, then the image has, to some extent, failed. This means making the images eye-catching and interesting. A little sense of humour is also often used to good effect, although Tell Tuttle, of the University of Strathclyde, UK, (whose work featured on the cover of the February 2014 issue), warned that you can go too far with the jokes: ‘you’re likely to be ridiculed for making pretty pictures.’
Layers upon layers
One cover in Chemical Science from 2014 stood out for me more than the others. This was not necessarily because it was the most eye-catching or the most information-rich, but because it piqued my curiousity. This cover from Tony James of the University of Bath, UK, was published last September and featured three stamps on top of a fluorescent image.
James says that good cover art ‘should be simple yet have a strong set of images telling a story related to the research.’ You can’t get much simpler than placing stamps on top of an image taken directly from the actual article. But there is obviously a story behind this image. The stamps featured are from the three countries of the groups involved; China, South Korea and the UK. Stamps also relate to sending messages, a nice (although a little tenuous) link to fluorescent imaging as cellular messaging.
At a casual glance, that is where the layers of information seem to end, but this cover goes further, although as it does so it does become a little obscure. James understates that ‘the next level may not be so obvious.’ The Chinese stamp is a painting of a tree peony, a native of China and used in traditional medicines as an antioxidant. The article describes the detection of peroxynitrite, which oxidises many biomolecules including DNA and unsaturated phospholipids. See the connection there?
The next stamp, from Korea, depicts the metric system, and the research involved taking measurements. I’ll admit that this link is a bit thin, but final stamp makes up for it. The British stamp shows a picture of Dorothy Hodgkin and celebrates 50 years since her Nobel prize for advances in x-ray crystallography and determining the structure of vitamin B12, another molecule with a role in cell messaging. The other two stamps are also from 50 years ago and 2014 was the year that the three corresponding authors all celebrated turning 50!
I love this level of detail and I have a great deal of respect for the story behind the artwork, even though I doubt that these subtleties are easily apparent to anyone not named in the author list. Nevertheless, special touches like these are certainly what interests me and what I believe make the difference between good covers and great covers.
Guest post by JessTheChemist
’I feel like I’d like to lead one more life. I’d like to leave a cultural imprint on society rather than just a technological benefit’ – Carl Djerassi
May you rest in peace, Carl Djerassi (October 29, 1923 – January 30, 2015).
The so-called ’father of the pill’ [he preferred ‘the mother of the pill’, as he saw himself nurturing the chemical ‘egg’ to bring forth the pill], Carl Djerassi, died recently at the age of 91 after a battle with cancer. Djerassi had a varied career involving both the sciences and the arts, contributing in particular to the fields of natural product chemistry, including antihistamines and pesticides, and spectroscopy. In 1951 Djerassi and his co-workers completed the synthesis of the first synthetic oral contraceptive, norethindrone or ’the pill’ and, due to the work by John Rock; by 1960 the pill was approved by the Food and Drug Administration for contraceptive use.
Djerassi was awarded a wealth of accolades for his contributions to the field of chemistry, from the Wolf prize in chemistry (1978) to the Priestley medal (1992); however, the Nobel prize in chemistry is a notable omission. Every year the twittersphere is awash with debates about the next Nobel prize in chemistry winner should be and Djerassi’s name is always top of the list, and my personal front-runner. The last will of Alfred Nobel stated that prizes should be given ’to those who, during the preceding year, shall have conferred the greatest benefit to mankind’. To say that the pill is of benefit to man- and womankind is an understatement and Djerassi should have been honoured many years ago by the Nobel Committee. As a small gesture to the man and his ground-breaking work, I shall celebrate him here. This blog series is focussed on the academic relationships of Nobel Prize winners, I’ve made an exception for a man who has had an enormous influence on my life and that of many other women around the world.
As with many other fine chemists, Djerassi is connected to a large number of influential and prize-winning scientists. His closest Nobel relatives are K. Barry Sharpless, who won the Nobel prize in chemistry in 2001 for his work on chiral catalysis, and Paul Karrer who won the prize in 1937 for this research into carotenoids, flavins and vitamins A and B2. Sharpless was a postdoc for Konrad Bloch who won the physiology and medicine prize in 1964 for his research into fatty acids and cholesterol. More information about Sharpless’ and Bloch’s connections can be found in a previous post about the academic family of Sir William Ramsay. Karrer was a graduate student for Alfred Werner, who himself won the Nobel prize in chemistry in 1913 for his research into coordination chemistry. Interestingly, Werner was the first inorganic chemist to win the Nobel prize. Karrer is also connected to George Wald, yet another Nobel laureate. Wald won the prize for physiology or medicine in 1967 for his work on the physiological and chemical visual processes in the eye. Through his graduate student, David Lightner, Djerassi is also connected to the 1930 Nobel prize winner in chemistry, Hans Fischer, a pioneer of haemin and chlorophyll chemistry.
Later in his career, Djerassi decided to become an ‘intellectual smuggler’, communicating scientific concepts through fiction and playwriting. Chemistry World‘s Ben Valsler spoke to him about this last year:
As you can see, Carl Djerassi is connected to a number of influential scientists from a variety of research backgrounds, and many more can be found at academictree.org. It is a travesty that Djerassi himself didn’t win the Nobel prize, but it is my hope that his legacy will continue for years to come.
Don’t forget, if you have a Nobel prize winning chemist that you want to see researched, get in touch with me via twitter (@jessthechemist).
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Guest post by Heather Cassell
In the lab, you develop a fondness for working with certain things: compliant equipment, pleasant smelling solvents, easy-to-culture bacteria. One of my favourites are fluorescent proteins – their bright colours can make even the dullest day that little bit more cheery. I find them a joy to work with not only because of their beauty, but because the source of that beauty also makes them easy to work with.
A good example of this is in protein production. During expression in E. coli, you often cannot tell how well expression of a colourless protein is going, but because fluorescent proteins will produce a colour even at a relatively low concentrations, it can be seen while the cells are still growing. This allows you to keep track of your progress, answering key questions like: do I have any protein? Or did I add the chemical I need to produce the protein? (The latter being a not uncommon mistake for a sleep-deprived scientist.) Getting answers to these visually means no lengthy purification procedure, avoiding the inevitable disappointment.
The colouration continues to be helpful as you go through the protein purification process: you can easily see if your protein has been released from the cells, whether it has bound to the column, if it has been released from the column and so on. Again, each of these steps requires another means of detection in colourless proteins.
Fluorescent proteins can also provide a splash of colour amidst a sea of colourless buffers, which allows you to immediately check you have added your protein. As you gain experience with these colourful concoctions, you begin to get a sense of what concentration they are just from the colour.
Fluorescent proteins not brighten up the lab and make protein purification easier, but they’re vitally useful throughout the sciences. They can be used to track the location and expression levels of other proteins in cells, to help produce difficult to express proteins, in fluorescence microscopy and in biosensors. But beyond their scientific merit, they can also be used to express your artistic side,
Guest post by Isobel Hogg, Royal Society of Chemistry
Can you explain the importance of chemistry to human health in just 1 minute? If you’re an early-career researcher who is up to the challenge, making a 1 minute video could win you £500.
We are looking for imaginative ways to showcase how chemistry helps us address healthcare challenges. Your video should be no longer than one minute, and you can use any approach you like.
The winner will receive a £500 cash prize, with a £250 prize for second place and £150 prize for third place up for grabs too.
Stuck for inspiration? Last year’s winning video is a good place to start. John Gleeson’s video was selected based on the effective use of language, dynamic style, creativity and its accurate content.
The closing date for entries to be submitted is 30 January 2015. Our judging panel will select the top five videos. We will then publish the shortlisted videos online and open the judging to the public to determine the winner and the runners up.
For more details on how to enter the competition and who is eligible, join us at the Take 1… page.