Thursday, 13 December 2012

Blog News: 1000 views!!

Well I've been going for a little while now, and whilst the posts have dried up a little recently (unfortunately academic commitments have got in the way), I've been continuing to update my list of chemistry help sites, and I've made a start on several posts, they just not quite been finished off.

Still, I've had a steady stream of views, and have now hit my first landmark, 1000 views! For the future, I'm hoping to find more time to write on here, and I've got a few topics in mind. I'm planning a series of posts defending molecules that get bad press (If you've got any suggestions of molecules to include; please leave a comment!), and I'll continue to cover the chemistry that makes the mainstream news, and anything else I happen to find interesting.

I've mentioned expansion before, and whilst the person I had lined up to cover biomedicine may no longer be interested, I'm still looking to get a couple of other on board, so we'll see on that front. If anyone wants to put themselves forward, please let me know.

Here's hoping I reach 2000 views as quickly!

Thursday, 22 November 2012

Correlation vs Causation

I recently came across this BBC article, which is a good example of correlation (most probably) without causation, but disappointingly, I feel the journalism lets it down slightly.

To quickly summarise the article, the BBC presents a graph of annual chocolate consumption and Novel price winners per capita, which demonstrates a very strong correlation, strong enough that there is only a one in ten thousand chance that the correlation doesn't exist. The BBC then presents several quotes from scientists saying that they believe chocolate helped them, before finally, right at the end, does it discuss the prospect that this is an example of correlation without causation, which is a common occurrence in science.

In a nutshell, just because a graph shows a correlation between two things, you can't conclude that one causes the other. Wikipedia offers a nice example: a correlation might exist between the number of deaths by drowning, and the number of ice creams sold. So one could conclude that ice cream consumption causes drowning. Obviously, this is ridiculous, a more likely explanation is that ice cream is sold more in the summer, the same time of year as more people are likely to go swimming in the sea. The more people swimming, the higher number of deaths by drowning. The rest of the wikipedia page deals quite nicely with the other types of correlation vs. causation, so is worth a read for anyone not familiar with the concept.

Back to the BBC article, by placing evocative quotes around the edge of the article, and saving the key scientific point until the end of the article, there's a risk that people who don't read to the end come away with completely the wrong message. Reading just a snippet of the article paints completely the wrong picture, which people could take the wrong way. Whilst there is some evidence to suggest chocolate can improve concentration, helping in study, taking it to extremes is obviously going to cause problems. Too much chocolate most likely has health implications that will far outweigh any gains in concentration.

Basically, this demonstrates the importance of effective communication in science, something I don't think the BBC have really succeeded with here. Leaving the main point to the end creates a significant chance of misleading people skim-reading the article, or not getting to the end. Now on a topic such as this, the risks are minimal, but take an important scientific issue, like nuclear fuel, for example. Say you want to tell people about new ways of dealing with spent nuclear fuel. Writing an article about the dangers of spent nuclear fuel, and the health issues it can cause, before finally concluding with "but actually, we've solved this now", runs the risk of giving people the wrong idea, and turning more people against nuclear power. Now the issue is not just people eating chocolate for the wrong reasons, you're impacting on public opinion of energy policy, which can have far reaching implications.

As always, comments, criticism and corrections are greatly appreciated. Thanks for reading.

Tuesday, 20 November 2012

Sports Drug Doping Part 2: How did we catch them?

So it's all well and good knowing what compounds are banned (part 1 is here for anyone who missed it), but how do the anti-doping agencies actually go about catching them? (Oh and if anyone would rather read about this in the literature, you'll find Chem. Soc. Rev. 2004, 33, p1-13 of interest, it's my main reference for the rest of this article)

Well firstly, cycling subjects athletes to more drug tests than any other sport. Drug tests are usually performed on urine and blood samples taken from athletes, either during events, or at random drug tests administered during breaks. Elite athletes have to constantly keep anti-doping agencies aware of their location at all times, so they can always be subjected to random drug tests. The first point worth making here is that the labs receiving the samples are given no indication as to who provided the sample. The samples are simply numbered, to ensure the integrity of the analysis. Also, when samples are collected, they are immediately split into 2 identical samples. The analysis is carried out on one vial, and only if there is significant evidence of a banned substance being used, is the second sample opened to confirm the result is genuine. As with forensic samples, there is a chain of paperwork associated with each sample, so that if suspicions are raised about tampering with the samples, everyone who has had contact with a sample is listed.

The labs themselves have to be up to an international standard. Wherever the Olympics are held, the IOC require that the host nation provide a dedicated drug testing facility, up to their exacting standards. For the 2012 Olympics, GlaxoSmithKline provided the state of the art facilities. By building a new facility every 4 years, a network of olympic-standard drug testing facilities is being established across the globe, providing testing facilities for other sporting events.

So once the samples are collected, and sent to the lab, what happens?

Well, urine samples allow detection of the majority of banned small to medium weight compounds, by fairly standard analytical chemistry techniques such as mass spectroscopy and gas chromatography. For larger molecules such as peptides and hormones (like growth hormones), a biological immuno-assay might be necessary.

Another complication is that to detect a molecule, and the amount at which it's present, an analysis has to take into account the effects the body has on the molecule. In some cases the molecule may be excreted intact, but others may be metabolised to smaller, or altered molecules, and of course some are between these two extremes. Once this is done, the work of an analytical chemist is to decide the best way to determine the quantity of each compound, and to accurately carry out the analysis. For most commonly detected performance enhancing drugs, standard operating procedures will exist to determine the amount present.

So how is the analysis itself carried out? Let's use stimulants as an example. Since taking stimulants can provide an instantaneous benefit in a race, they must be detected fairly quickly. Many stimulants are closely related structurally to amphetamine, giving them similar properties. By tailoring conditions to match these common properties, it is possible to extract most likely stimulants from a urine sample. In the standard protocol, this is achieved by extracting into a solution of ether at a pH above 9.5. This sample can be tested by GCMS (Gas Chromatography coupled to Mass Spectroscopy), to comfortably detect amphetamines at a concentration of 500 ng/mL.

What happens to athletes who test positive? Well, it depends on the sport. Currently, an athlete found guilty of doping by WADA receives a 2 year ban for a first major offence, with a life ban for a second offence. But WADA want to increase the ban for a first offence to 4 years. Different authorities however have different rulings and the recent events surrounding Lance Armstrong further complicate matters. Those who implicated Lance Armstrong in confessions to USADA appear to have been given significantly reduced bans, with some only receiving winter bans, which will have little effect on them competing. Whilst Armstrong himself was banned from professional cycling for life.

What about the future? Well the gains offered by doping will always appeal to some, but increasingly complicated doping programs will be necessary to outwit the authorities using the current drugs available. However, the idea of 'designer drugs' could make things very difficult for the testing agencies. A few years ago, Canadian customs officers seized bottles containing a drug called desoxy-methyl-testosterone (DMT). Analysis showed it to be a designer steroid, with similar effects to testosterone, but a drug which would never have shown up in a drugs test at the time. The spectre of this will always hang over elite sport. The development of new drugs can't be predicted, so testing agencies are reliant on obtaining samples of the new drug before they can begin to test for it. With enough money, it would be possible to both create a new drug, or obtain exclusive supply, and to rigorously keep it safe, so that drug testing will be kept in the dark, allowing those cheating to escape without detection.

So can we ever be sure sport is free of drugs? Well, the simple answer is no. The recent revelations about Lance Armstrong seem to have left a bad taste in the mouth of many elite athletes, such as Bradley Wiggins, and many teams too have come forward as being actively anti-doping, with hardline policies on it. But, whilst it is becoming increasingly difficult to dope, some will still keep trying.

Apologies for the delay in writing this, uni has kind of got in the way recently. As always, any comments/criticisms/corrections are greatly appreciated.

Friday, 2 November 2012

I couldn't resist tearing this to pieces...

"Rawforbeauty" uploaded this picture on facebook a while ago, but I've only just seen it:

Wow. So the first question is, where do we start? Oh, and actually, before I do, I should probably point out that I don't work for, or have any connections to, any large pharmaceutical, agrochemical, etc company, I'm just a chemistry student concerned about the propagation of chemical mis-information. Anyway...

I could argue that Pfizer don't (to my knowledge) own Nutrasweet, with Monsanto themselves stating that the business was sold to J.W. Childs Equity Partner. I could also argue the reason it was sold was purely economic as Aspartame has been off patent in the EU and USA since 1992, and it's perfectly logical to sell a business with little money left in it. But, this blog is about science not economics, so I'm going to focus on debunking the claims in the paragraph of lies at the bottom:

  1. Fluoride occurs naturally in a lot of tap water, and in some areas where the natural concentration is low, it is added. There is a lot of medium to poor quality research on this, but it has been analysed and what conclusions can be drawn are summarised in this paper. They conclude that the presence of fluoride in tap water helped to reduced caries and tooth decay in children. There was some evidence of increased fluorosis (normally harmless, and in most cases barely noticeable, white streaks in tooth enamel), and crucially, the study concludes "No clear evidence of other potential negative effects was found". Clearly, it is baseless to call fluoride in tap water a poison.
  2. Is Aspartame poisonous? In a word - no. If you want more than that, then this MSDS summarises it quite nicely: "A vast database exists regarding the safety of aspartame in man.  Oral doses of 75 mg/kg/day to human subjects for 6 months did not produce any clinical signs.  The Acceptable Daily intake (ADI) approved by the U.S. Food and Drug Administration (FDA) is 50 mg/kg/day.  The oral LD50 in rats is >5000 mg/kg (practically nontoxic).  Inhalation exposure of male and female rhesus monkeys to aspartame at concentrations up to 16 mg/m3, 6 hours per day for 14 consecutive days, did not produce any consistent treatment related effects" - I really don't think I need to say any more, but if you want even more reassurance, this is a pretty good read.
  3. If you're going to use 'scientific data' to back your claims up, at least make sure it stands up to scrutiny. For a start, only one study (without proper reference) is mentioned, and with a sample size of 7, it's hardly convincing. It's also interesting that when looking online, I can't find the paper itself, only lots of people damming aspartame and using it to support their case. Sadly, without the paper, I can't tell you just how well designed the experiment was, irrespective of the tiny sample size. But, let's take a look at the literature properly, and find a nice, recent, peer-reviewed article, which states: "The studies provide no evidence to support an association between aspartame and cancer in any tissue. The weight of existing evidence is that aspartame is safe at current levels of consumption as a nonnutritive sweetener." and "Critical review of all carcinogenicity studies conducted on aspartame found no credible evidence that aspartame is carcinogenic." Personally, I find that pretty reassuring.
  4. Yep, Aspartame is manufactured from phenylalanine, which is produced by genetically modified e-coli to produce it as a by-product. Well done- but that's as good as it gets. GM bacteria are used to produce a whole host of products, the most well known being insulin, I don't see too many people complaining about using GM bacteria (which are probably e-coli derived) to save the lives of hundreds of thousands of people, or calling for a return to the bad old days where insulin had to be extracted from cadavers of pigs and cows. This has a moral or religious concern for many people, as well as issues of rejection, and reduced efficacy. (Although, I'm getting away from my argument now). Back to E-coli. Firstly, most strains of e-coli are perfectly harmless, and many strains are found normally in the gut of healthy humans and animals. I don't have a problem with this being modified to produce my sweetener. Especially as heat treatment, purification, etc, will kill and remove the bacteria long before it gets anywhere near me.
  5. Defecating aspartame? Don't make me laugh. Defecating usually implies some kind of gastro-intestinal tract, which clearly bacteria don't possess. The process could be described as being equivalent to breathing or photosynthesis, but that doesn't make for quite such a catchy soundbite. Nobody is complaining that the oxygen we breath has been "defecated by plants", so quit moaning about this too, or at least be consistent in your opinions and eliminate oxygen from your daily diet too.

Basically, the whole image stinks of a 'chemicals are bad and should be banned' attitude. I'd be surprised if people who believe this ever read my argument above, even moreso if they follow the links to respectable sources, and be over the moon if realise that maybe their belief isn't supported scientifically, and should think about changing it. Sadly it wouldn't surprise me at all if they pay absolutely no attention and continue to advocate banning something there is little evidence to show is dangerous. Have these people heard of the risks of dihydrogen monoxide? It's possibly one of the biggest killers in the world today, and I guarantee you'll find it in every single human being on the planet.

This kind of post isn't really what the blog is about, but if one person reads this and changes their opinion, then it's worth it. I can't stand 'chemophobia' (a common theme amongst chemistry bloggers), so if anyone spots any other examples of this kind of rubbish then leave a comment, and I'm more than happy to tear each one to pieces (there's easily enough out there to make a series of posts out of this).

Oh, and as always, if you find a fault, want something explained further, or have anything else to say, leave a comment and I'll get onto it.

Thursday, 25 October 2012

DIY Lab Equipment?

A drill-powered centrifuge, your own personal pharmacy or made to measure prosthetic limbs, 3D printing has come a long way since the fuss about custom chocolate. As this is first and foremost a chemistry blog, how does 3D printing work, and how can it revolutionise chemistry?

So firstly, how do we go about printing in 3D? The cheapest RepRap 3D printer currently retails at £749. This allows users to print with 2 types of plastic, acrylonitrile butadiene styrene (ABS), and Poly(lactic acid) (PLA). Users either download designs from repositories like Thingiverse, or create their own design in 3D software like SketchUp. Many different types of printing are possible, the RepRap using a technique called Fused Deposition Modelling (I think we'll stick with FDM). In FDM, filaments of the desired plastic are wrapped into coils (think 3D ink cartridges), and when required drawn into a nozzle. This nozzle is heated, so the plastic melts. A computer directs the nozzle in 3 dimensions, so the melted plastic is placed exactly where required. Once the plastic is out of the nozzle, it cools and hardens, to form part of the 3D object.

So you've got your printer, stocked up on filament, now what? Well some of the simpler chemistry designs available are for common lab gear like Buchner Funnels. However, if I wanted a plastic Buchner funnel that'll likely dissolve at the first sign of an organic solvent, forking out £749 for a 3D printer wouldn't be my first idea. £749 is enough to keep even me the clumsiest of chemists in Buchner funnels for life. So far then, a 3D printer doesn't look like it's coming to a lab near you any time soon, so what else can it do?

The simplest, genuinely useful piece of lab equipment I've seen (and I'd love to hear about others) is the DremelFuge (video in the first link), for the price of a drill, and a few grams of plastic (I make it about £60), you've got yourself a basic centrifuge capable of speeds up to 33,000rpm - which is getting into "ultracentrifuge" territory. Need a handy centrifuge for field work? Forgotten to balance your lab's centrifuge and written off a £1000 piece of kit? Suddenly the DremelFuge sounds pretty attractive.  Whilst I'm not suggesting selling your bench-top centrifuges and heading down to B&Q, for labs on a budget, hackerspaces for examples, you're opening up avenues that wouldn't previously have been possible without serious funding.

But yes, most labs that need one already have a perfectly good centrifuge, and whilst it shows 3D printing can potentially save costs (especially when you've already taken the initial hit on the printer) its not shown it can truly innovate yet. What about your own personal pharmacy?

That's just what the Chronin group at the University of Glasgow have been doing. Using an adapted 3D printer, they've developed techniques for printing reaction vessels, with the chemicals already inside. By inserting electrodes, they were also able to produce an electrochemical cell. Next (and this is where 3D printing becomes really interesting), they found that the shape of the vessel determines the products formed. As proof of concept, they've used this to synthesise some novel heterocyclic molecules, with the printed reactor vessel an important part of the synthesis.

Finally, their pièce de résistance, is reaction vessels that play an active part in the reaction. By mixing a Pd/C catalyst into the plastic used to fabricate the reaction vessel, the vessel could be used to hydrogenate styrene to ethylbenzene in around 30 minutes at room temperature.

So where's this heading? Cronin's group envision a situation where you combine some biotechnology into this too, and create a one-piece home lab, where you give it some cells, it works out what diseases you're susceptible to, produces a drug to cure it, and all before you've even developed a symptom. We're not quite there yet, but that's something pretty awesome to aspire to.

Sticking with their catalytic vessels, they also suggested using it so patients can make their own drugs at home, from a common starting material. Imagine it like a Rubik's cube. You buy your starting material from the supermarket, and stick it in the top. Each block in the Rubik's cube is impregnated with a different catalyst, so by directing your starting material from square to square, you'd be able to transform it in different ways. I can imagine a situation where you look up a recipe for, say, Bupropion, with instructions like, "twist top of cube to the left, rest on it's right side, then leave in the microwave for 10 minutes".

Give it 10, maybe 15 years and if I was a pharmaceutical company, the DEA (it's not hard to think of some illicit applications, is it?), or, sadly, your friendly departmental glass-blower, this technology would be starting to worry me, because the possibilities for 3D printing really do seem to only be limited by human imagination.

For more on the work of the Cronin group, this BBC video is a nice introduction, the RSC have a decent article here and the groups paper is also available here (if you've got Nature Chemistry access - unbelievably my uni don't). For more on 3D printing, there's a nice article in Science magazine (again, pay-walls, sorry).

As usual, any comments or questions would be much appreciated. If you spot a mistake, or feel I've missed something, let me know. Anyone wondering where the second part of my Sports Drug Doping series has got to, it's coming, I'm still gathering material. There's a follow-up to my Petrol from Carbon Dioxide blog in the pipeline too-when I've found out how many cows are on the planet (all will become clear!).

Monday, 22 October 2012

Chem Coach Carnival: UK Undergraduate

I figured a lot of the contributions to See Arr Oh's Chem Coach Carnival would be about the higher end, amazing jobs you can get through chemistry. Most (all?) of these people would have started their careers as undergraduate chemists, and as I'm a current undergraduate (UK-based), I figured I'd start there, and ask the question:

How do you get onto a chemistry degree program?

If you're currently a high school student (GCSE's)...then firstly well done on having some idea what you want to do with your life! There's not much to worry about right now, but when choosing A-levels, if a teacher tells you "take the subjects you enjoy"-pay absolutely no attention at all. (Note: This is actually decent advice if you have no idea at all, but no good if you've made your mind up) If you know you want to do chemistry, but happen to enjoy History, French and English too, then whatever you do: don't take this combination! Most, if not all, chemistry departments in the UK require at least AS-level Maths, and another science besides Chemistry at A2 (ideally Biology or Physics, preferably both). If you want to study Chemistry, you really must start your A-levels studying Chemistry, Maths, Biology/Physics, and then you can probably get away with a free choice on the last one. 

Besides that, work hard, and don't neglect GCSE English, you'll be in a world of pain if you don't get a C.

If you're currently studying for AS-levels...assuming you've followed the advice above, you're all set to apply to Chemistry at university.* My first advice is that it's never too early to go to open days. Some uni's have open days in June/July, and then again in September. The earlier ones can often be quieter, and it gets your mind thinking about university. Uni's often monitor attendances at open days, so showing an early interest is only going to be a point in your favour. If you can think of a question to ask, ask it, but don't worry about being too shy - most people are. I've given a few open day department tours, and the amount of people who say nothing is crazy high, so don't worry about it.

If you can get any chemistry-related work experience, jump at the opportunity, however mundane it looks; chances are like gold dust, so it'll help your uni application stand out. Other than that, reading around your subject is very important, especially when it comes to interviews (more on those delights below). Seriously, at least read Bad Science at a minimum [If anyone can suggest any others, I'll post a list at the bottom of the page]. Work on your personal statement over the summer, they can be hell to write, and the sooner you get your UCAS application submitted, the better. A lot of uni's offer places on a first-come-first-served basis (assuming you're good enough)

So you've applied....firstly-well done! It’ll be a while before you hear anything, so relax and keep reading.

Aargh - interview! Ok, so I've instantly displayed the wrong emotions, interviews are nothing to be worried about, relax! The academic involved isn't (usually) trying to catch you out; they want to let you show what you know. If you mentioned any extra reading in your personal statement, re-read it before the interview. It's also worth reading a bit ahead in your textbook if you can. Most chemistry syllabus' cover the same material, but in a different order, so don't be too surprised if an academic asks something you haven't learnt yet, they simply don't know you haven't done it. If you can answer, have a go, but it might be worth starting with "So we haven't covered this in class yet but...", to give yourself a margin for error.
Whatever you do, don't try and BS an academic! To my error, I tried this one - learn from my mistake! In my personal statement, I mentioned the toxin Ricin, and the assassination of Georgi Markov. My interviewer asked me how Ricin worked. I couldn't quite remember, but I went for it, and said something that was part-truth, part-guess and part utter tosh. He simply smiled at me and moved on. At the end of the interview, he had a hunt through his bookshelves and dug out a copy of a paper, asking me to read it before my next interview. I sat there in the waiting room, reading a paper written by the interviewer himself, on the precise manner of ricin bioactivity. Needless to say, I didn't get an offer.

Other than that, good luck with getting on the next step to your dream job in chemistry!

Other Books: The Poisoner's Handbook; Copies of New Scientist, Scientific American...;

*If you're looking at this, don't panic if you haven't got the right subject choices, and it's too late to change. Take a look at foundation year courses, or see if your sixth form/college will let you stay on another year so you can take the right subjects. 

Saturday, 20 October 2012

Sports Drug Doping Part 1: What's banned?

In the wake of the recent controversy surrounding Lance Armstrong, and many other high profile cyclists from the 2000's, I thought it might be worth talking about how anti-doping authorities, such as WADA and USADA go about catching drug cheats. This area has been covered in the literature frequently, and this paper provides the basis for this blog, but unfortunately it'll be hidden behind a pay wall from many people. So firstly, what are they testing for?

 Well basically, any substance artificially introduced to the body which provides an advantage to athletes, whether natural or artificial. WADA (the World Anti-Doping Agency), in conjunction with the International Olympic Committee (IOC), have published a list of banned substances and techniques, which outlines the types of drugs banned, with examples of each.

Prohibited Substances:

Athletes are never allowed to test positive for these drugs, with an unexplainable positive usually resulting in a ban. The categories are:

  1. Non-Approved Substances: If a drug hasn't been approved for human use by a government health authority, it can't appear in samples. The is to prevent athletes taking designer drugs, dangerous drugs which have been banned, or drugs only approved for veterinary use. This means drugs which aren't safe for humans (or the safety is unknown) should never be taken by athletes.
  2. Anabolic Agents: Otherwise known as steroids, these are drugs designed to increase the size of muscles faster than is naturally possible. Examples include 1-androstenediol, a potent muscle building enhancer. These drugs mimic the effects of testosterone and other steroid hormones on the body.
  3. Peptide Hormones, Growth Factors and related: Like steroid hormones, these are naturally produced in the body, but are also artificially introduced for a variety of reasons. This category is home to the infamous EPO (Erythropoietin). EPO aids in the delivery of oxygen to muscles, by increasing red blood cell production. This gives a significant increase in VO2 max for the athlete.
  4. Beta-2 Agonists: Many drugs in this category are actually prescribed for asthma, so afflicted athletes are allowed to test positive up to the recommended dose. Although, there is evidence (apologies for the pay wall) that the restrictions may actually hinder asthmatic athletes. These drugs are powerful bronchodilators, helping to open up the lungs (hence their asthma use). When inhaled, the drugs have only a significant impact on the lungs, but when injected or used in tablet form, they may act as anabolic agents, which is why they're banned.
  5. Hormone and Metabolic Regulators: Actually some of these drugs are often used to treat breast cancer (such as Tamoxifen and Anastrozole), but would be taken by elite male athletes to disguise the physical impacts of increased testosterone levels. Abnormally high testosterone in the body is converted to estrogen, leading to gynecomastia (or man-boobs).
  6. Diuretics and masking agents: Anything designed to give an artificially low test result, or increase secretion of drugs from the body, is banned. Infusing saline into the blood stream helps to dilute the blood, giving lowered test results.
Banned Techniques:

In additions to banned drugs, certain techniques are banned too. Reintroducing blood is the technique which has made the most headlines. Athletes have blood removed prior to an event, then reinfuse it at a critical moment, boosting performance. Other banned techniques are introducing artificial oxygen carriers to the blood, or manipulating the composition of blood. Gene Doping, introducing nucleic acid polymers, is banned, as is introducing genetically modified cells. It goes without saying that it's also banned to tamper with samples.

Drugs banned during events:

So the above drugs and techniques are banned at all times, whilst other drugs are only banned during events. These include stimulants (like Caffeine), narcotics (like morphine), Cannabinoids (natural Cannabis or synthetic THC), and glucocorticosteroids (prevent inflammation, helping injury management). In some sports, alcohol and beta-blockers are banned too.

So now we know what's banned, the next question is: "How do we detect them?", and hopefully the next blog will answer that.