Top 5 Tips For Writing Your Thesis.

BACKGROUND

There comes a point in every Ph.D students life where they have to leave the lab and chain themselves to a desk for a couple of months for the final write-up session. This can result in a mixture of emotions, initial elation at the thought of getting everything finished, anxiety when you can't seem to write more that 50 words in a day, and sheer frustration as you try convince MS word to allow you insert a single landscape page amid a multitude of portrait orientated cousins. Despite completing my Ph.D 4 years ago I remember my own experiences of writing up as if it was yesterday. During my write-up I discovered a couple of techniques that helped me keep writing, and manage my data well. I'd like to share my own experiences of what helped me. I'm omitting the obvious things like setting targets, proof-reading, or getting your peers to review your work. Instead I will discuss the less obvious. 

TIP 1 - USE MENDELEY FOR REFERENCE MANAGEMENT

I've devoted a whole article to this topic before so I won't go into detail here. What I will say is that Mendeley is a superb piece of software for reference management. It's far more easy to use than Endnote, it's free, and it's packed full of useful features. That's pretty much it in a nutshell.

TIP 2 - TRY TO BREAK MS WORD

This sounds counter intuitive I know but I promise you this is a good idea. Allow me to explain. When I was writing my thesis I was using word 2007, which at the time was a big improvement on word 2003. I had written my undergraduate thesis on word 2003, and I ended up changing over to openoffice because it was such a hateful experience otherwise. But I was assured by my colleagues that Word 2007 was actually usable so I thought I'd give it a go. I was still wary because I intended to have a lot of images and equations in my thesis, and one of the main problems with 2003 was how poorly it responded to trying to insert/re-size images and equations. So, before I embarked on using Word 2007 at all I decided I need to know its limitations. What forces it to stop working, and in what way does it stop working? For example, here are some of these tests I did. 

• Equations: I began by entering a simple equation. I wanted to see how Word handled problems like inserting Greek letters, centering an equation in the middle of a page, or labeling it "eqn" for example. Word 2007 could handle most of this, I could use Greek lettering, I could center the equation in the middle of the page, and I could label it, but the label did not line up with the equation itself! That was pretty frustrating. Eventually, a clever colleague of mine realised that if you inserted a one row, two column table the width of the page, you could insert an equation in the left hand column, and the label in the right hand column. You could then remove the lines so it looked like it was aligned correctly. We never did find a better way of doing this. But thankfully we discovered this in the early stages of writing up so inserting equations was only slightly painful.

• Document Structure: There's a reason people use word processors. They are designed to speed up the process of writing, make editing quick and easy, and automate some of the more tedious processes. But actually most people who used Word to write their thesis did not take advantage of many of its useful functions. For example, being able to automatically generate a table of contents and a table of figures is incredibly useful. To do this you need to use section headings and you need to let word manage the naming of your figures.  It can be tricky to set up but open a new document and experiment with the section heading formatting. Check what happens to your numbering when you add or remove sections, check what happens when you add your table contents. Once you set up your document correctly you will be able to generate and more importantly update your table of contents and table of figures in a few seconds! Two friends of mine writing up their Ph.D at the same time as me never did this. This meant they were manually writing and numbering section headings. Every time they added or removed a page they were manually updating their table of contents to have the correct page number. This is not how a word processor is supposed to be used. It's extremely time consuming to operate this way, and it takes valuable time away doing what you are trying to do, writing your thesis.

TIP 3 - USE DROPBOX/GOOGLE DRIVE

This one is non-negotiable as far as I'm concerned. There are a multitude of options when it comes to backing up data, TimeMachine for Mac, or File Recovery for Windows, SD cards, USB keys, and email. Trust me, Dropbox or Google Drive are the best options for you. Personally I have a better experience with dropbox so this is what I will discuss.

To give you an idea of why cloud storage is much more effective than anything else allow me to demonstrate my computer setup. During the last year of my Ph.D I went through three laptops while I was writing up. The first two just stopped working without any warning. The screen broke on one, and the motherboard broke on the other. Laptop no.3 was a gift from my supervisor and while it worked very well, and allowed me to continue to have some mobility it did have a tiny 13" screen. This is not ideal when you often want to look at multiple sources of information. So sometimes I would work from home on the weekends and use my own desktop to avail of a much bigger screen, and sometimes I would work from my Linux desktop in work since it was to only way for me to generate data from computer simulations. This means I used a total of five computers, three of which were in regular use depending on my needs. Trying to manually sync your data between all of these would have been a nightmare without cloud based storage.

By using Dropbox all I had to do was have one folder called "Thesis" and save my active word document in there. Once I opened my word document from Dropbox and set word to autosave every 5 minutes it didn't matter if any of my computers broke. I could simply move to any other computer on the planet, login to my Dropbox account and continue to write with all my images, data, and research papers right where I left them. I didn't have to spend any time making backups, moving files to SD cards, or emailing anything to myself. I didn't have to do any version control and I never once lost any of my work, despite the best efforts of MS word. It was easy and stress free. In addition to all of the backup benefits there is one more very useful benefit. If your supervisor wants to see the latest version of your document you can simply share the relevant folder with him. He can access it anytime he wants, and any changes he makes will be saved on the version you are working on. This setup has worked really well for me. Do it!

One final word on this. I have written about the reference management tool Mendeley in the past, see here. Mendeley give you a small amount of cloud space (500Mb) to store and sync your research papers. However, I quickly went over this limit, so to circumvent this I found it was much better for me to create a Dropbox folder for research papers and save all my journal articles there. I could then point Mendeley to this Dropbox folder and it would always have access to all the relevant papers no matter which computer I used.  

TIP 4 - USE PLENTY OF IMAGES

Pretty much everyone I knew got writers block at one time or another. It doesn't just happen to professional full time authors. It happens to anyone writing on a particular topic for a long period of time. Different people have different solutions for this, but personally I found that inserting a image really helped me to re-focus my attention and clarify what I wanted to say. The problem with writing a thesis is that's it is very specific and sometimes you cannot find an image you need to describe a particular process. In this case I would actually make my own images using PowerPoint. I know this probably sound labour intensive, but actually you can make great images using very simple shapes and the more you do it the faster you will become. Also, because you are making the image if forces you to think about the process you are trying to describe, and this often leads to a re-write of the relevant text. The resulting combination of a specific image, and well written text means both you and the reader understand the topic much better.

Even if you don't make your own images it is important to utilise them to help you make your point. They should always be there to add clarity, demonstrate an abstract principal, or summarize information you have said, or are about to discuss. Well used images can really demonstrate your ability to explain and understand complex ideas. 

TIP 5 - WRITE WITHOUT RESTRICTION

As a scientist writing about peer reviewed scientific theories and concepts I found it necessary to qualify every sentence I wrote, unless I was making it clear that I was stating my own opinion. Even then my opinion must be based on fact established somewhere else in the literature. This meant that for the first few weeks of writing up I would end up writing one sentence like, "All proteins are made of amino acids of which there are twenty naturally occurring types" and then agonizing over how we/I know this to be true! I'd trawl through the literature looking for similar statements and after hours would only just about be in a position to verify this (it turns out there are actually 22 naturally occurring amino acids). However, it is just not practical to question every piece of information you think you know. After a few weeks I was writing without this kind of restriction, I trusted that the statements I was making must be based on evidence, and I was definitely going to provide evidence for all the claims I was making, but that would come after I completed that particular section. So after finishing a couple of paragraphs I would then go back over it inserting the relevant references. If I came across something I could not find any evidence for in the literature I would have to re-write it based on the evidence that was available in the literature.

Overall, by trusting that you do know what you think you know you can actually get stuck into describing the really important and heavily theoretical/abstract aspects of your work. Modifying a sentence to say there are 22 amino acids instead of 20 is really really quick! And this was something I definitely didn't appreciate before I started writing.

CONCLUSION
There are some valuable tools out there to help you write up and remove some of the unnecessary stress. Get to know the software you use. Know their weaknesses, and be prepared to spend a small amount of time at the start to prevent a lot of time being wasted later on. Writing up can be fun. It's very satisfying to close your laptop at the end of the day and know you've made good progress that will sill be there in the morning no matter what happens. 

Innovative Ways of Treating Waste Materials

BACKGROUND

When it comes to government funding, spending on scientific research is always easy to cut. Generally speaking the public won't notice or care very much, and it could be years before the effects are fully realised. In 2014, Ireland increased public expenditure on science to €2.7 billion, up from a figure of €1.8 billion which has remained fairly constant over the last 5 years, see here. Increased funding is always welcome, but those performing the research are under more and more pressure to show the practical implications of their research. Science is about more than the latest mobile device, or faster download speeds. There are practical applications spinning out basic research all the time. This blog post uses the backdrop of Irelands agricultural sector to show two innovative ways in which improved understanding of science is helping to reduce waste, and improve sustainably.

AGRICULTURAL WASTE IN IRELAND
The normal day-to-day operations of an Irish farm can produce a wide variety of waste products, from tyres, to engine oil, plastics, and old chemical fertilisers.Those than can be recycled or reused often are and Ireland has made great strides in this area in the past decade after lagging behind many of our european counterparts.

Most recently there has been a major initiative to collect hazardous waste materials from Irish farms. The environmental protection agency, EPA, has been very active in this regard, setting up waste collection points at ten strategic locations around the country in an attempt to clean up our farms.

DANGERS OF AGRICULTURAL WASTE

A typical Irish farm uses an increasing number of chemical products. These chemicals are safe when used and housed appropriately, but they could pose a serious threat to the environment or to a farmer’s health if not stored or disposed of correctly. One example is that of chemical fertilisers high in nitrogen and phosphorous. An uncontrolled release of fertilisers into a nearby water supply will result in the formation of algae blooms rendering the water uninhabitable for marine life. The presence of veterinary medicines and equipment such as anaesthetics, painkillers, and syringe needles can also pose a risk to the farmer or his family. Each of these medications must be stored correctly, securely, and safely disposed of when no longer in use. Thanks to the efforts of the EPA information is available to farmers on how and where to best dispose of these hazardous waste materials.

CURRENT REGULATIONS ON WASTE DISPOSAL

The establishment of hazardous waste collection points by the EPA was performed in collaboration with Teagasc and local county councils. This is in accordance with the National Hazardous Waste Management Plan, 2014-2020, which aims to prevent waste, as well as reducing it. This plan was well received by Irish farmers, pleased to have a means for the safe disposal of their waste material.

AQUACULTURE

It’s not just Irish farms that produce waste by-products. The Irish fishing industry is an essential source of income to our more remote communities. For many, fishing is more than just a traditional way of life. The fishing industry in Ireland represents a thriving and important economic activity with revenues in excess of €850 million per annum. 

Exports from Ireland find their way as far afield as Russia and China. Total revenue is expected to hit €1 billion by 2020 thanks to the recent and welcome news of increased government investment in this sector. The minister for Agriculture, Simon Coveney, announced €241 million worth of investment in the seafood sector to stimulate jobs and develop the industry, as well as to win new contracts. There is also an emphasis on environmental impacts and conservation measures to help sustain and conserve this important industry for future generations. Sales of shellfish account for 20% of all seafood revenue, of which shrimp and crap are a significant part. 

Currently, both shrimp and crab are undergoing processing to remove the edible meat from the inedible shellThis results in a vast amount of unusable waste material. Incredibly, over 6 million tonnes of waste material are produced worldwide, every year. The shells of these crustaceans are composed of a strong biological material called chitin, shown below. 

Chitin has some very desirable properties for the animal that produces it. It’s lightweight but tough and durable. It is secreted from the skin of the animal, meaning each shell is custom made and fits perfectly. However, in terms of human consumption, chitin is a useless by-product of shellfish processing. However, modern biomolecular science provides an innovative use for this otherwise useless by-product.

CASE STUDY I - ERRIGAL BAY

Errigal Bay, an Irish-based seafood processing company with plants in Donegal and Wexford specialises in shellfish processing, with established markets in the US, the UK, and Asia. In 2012 they teamed up with Letterkenny Institute of Technology (LYIT) and with the help of EU funding, began researching a better way to treat shellfish waste. The ChiBio project, as it’s known, was born. This partnership between industry and academia set out to turn chitin into a useful, and profitable product in it’s own right. Thanks to advancements in modern biology, scientists at LYIT are working on turning chitin into a new product called Chitosan. Chitosan is obtained from chemical modification of chitin to obtain a unique biopolymer with fascinating characteristics. The most exciting properties of this product are its biomedical applications, where it is currently being utilized for everything from promoting bone growth, to wound dressings, and even artificial skin. 

Until recently manufacturing Chitosan from chitin was expensive and environmentally damaging. But researchers at LYIT have been able to build on a growing body of scientific research in this area to make Chitosan production a cleaner and greener process. It’s all thanks to the applications of molecular biology to create genetically modified microbes capable of munching on chitin and generating Chitosan in the process. Dr. Catherine Lynch heads the research team working on the ChiBio project at LYIT. She spoke about the importance of Chitosan production in terms of reducing the waste that Irish shell fishing produces, “The fishing industry creates a major source of biowaste in Europe. The legislation calls for marine biowastes to be disposed of in landfills. This is expensive and not environmentally friendly.” Dr. Lynch found the research both challenging and stimulating. As for her motivations, she states, “The major incentive was to use raw material that was considered waste and produce a valuable product such as Chitosan. The main challenge was to generate enough material for our EU partners to work with”. Thanks to the work of people like Dr. Lynch, Ireland can expect to reap significant benefits from Chitosan in the future.

CASE STUDY II - BIOPLASTECH

Plastics are ubiquitous in every aspect of modern life, and farming is no exception. From pesticide containers to fertiliser bags, Irish farmers dispose of 25,000 tonnes of waste plastics every year. Off all the plastics used, polyethylene (PE) is the most common, being used to make piping, chemical storage containers, and agricultural films.

However, as governments and businesses alike begin to appreciate that oil reserves are limited, is it now time to rethink how we make and use plastics. A young Irish company appropriately named Bioplastech aims to do exactly that.

Bioplastech aims to convert waste plastics into what is known as bioplastic. By screening through hundreds of microbes found in local soil, Bioplastech struck gold, or rather plastic, when they identified a stain of bacteria called Pseudomonas putida. Headed by Dr. Kevin O’Connor at UCD, the company’s scientists grow these bacteria under laboratory conditions using a special diet of glycerol and polyethylene (PE). As the bacteria feed and grow they convert PE to a new biodegradable plastic called polyhydroxyalkanoate, or PHA for short. Amazingly, research has shown it is also possible to produce PHA from common-or-garden ryegrass, a plant that Ireland has in abundance.

It might seem counterintuitive to make bioplastic from existing plastic materials, but this strategy makes sense for three reasons. Firstly, there is an abundance of PE plastic. Currently this material is either sent to landfill sites or simply warehoused until it can be incinerated. Both of these waste streams are harmful to the environment. By using PE to make bioplastics, the amount of harmful plastics being sent to landfill can be dramatically reduced. Secondly, traditional plastics are made using petroleum, which is derived from crude oil. With finite oil reserves it makes economic and environmental sense to utilize the vast amount of waste plastic already available for the production of bioplastic. This reduces the global demand on oil supplies. Finally, bioplastic is biodegradable, meaning it can be safely disposed of in landfills, or recycled as a starting material for more bioplastic. Overall, the production of bioplastic has a positive impact on the environment, while at the same time highlighting a high-tech and innovative home-grown industry.

THE FUTURE OF WASTE DISPOSAL IN IRELAND

Irelands environment is one of our most valuable assets. The Irish landscape is recognised worldwide for it’s breath-taking scenery and idyllic countryside. As a nation we have worked the land and trawled the sea for generations, all the while maintaining the natural beauty of this unique land. The industrialisation of farming and fishing was necessary for Ireland to remain competitive and productive. We must continue to be mindful of our impact to the environment moving forward, and build on the continued success of the EPA in reducing and reusing waste materials. Clean waters and uncontaminated land are essential to our continued economic success as a country.

The education and industry sectors also have a role to play. Continued government investment in the biosciences will ensure Ireland has the expertise required to drive innovative waste management solutions. Errigal Bay and Bioplastech are both great examples of what can happen when industry and universities work together.

My Experience of Finding A Job After My Ph.D

MY BACKGROUND

I completed my Ph.D. biochemistry in August 2011. After 4 years of hard work it felt great to be finished, in fact it feels a bit like this. I had of years of laboratory based research experience supplemented by extensive undergraduate teaching duties. I considered myself skilled and experienced in experimental design, data management/analysis, managing work flow, direct supervision of undergraduate projects, and teaching, in addition to the use of modern molecular biology techniques, and biochemistry used in the expression, purification, and characterisation of proteins. In short, I was educated, and experienced. I wanted to stay in Ireland, but I had to acknowledge most of the work for post-doctoral research was overseas.

TRANSITIONING TO POST-DOC RESEARCH

My initial job applications were focused on post-doctoral research opportunities in my field and focused mainly in the UK. While there was a constant stream of relevant positions coming online it quickly became apparent that without a firm experimental background in structural biology my current skill-set was not enough to secure a position. So I changed tactics, and began applying for research assistant positions. These positions can require less experience and expertise and are an excellent way to transition between two specialities. You become skilled in new techniques while maintaining your competency in general laboratory skills, and your employer gets an experienced scientist at low cost that will become proficient very quickly, it’s a win-win situation. However, on the few occasions where applications resulted in interviews I was dismissed as either not being skilled in what they wanted, or not being taken seriously because why would a Ph.D. apply for such a position, clearly, I was going to leave at the first opportunity contracts, responsibility and professionalism be damned!

PLAN B - INDUSTRY APPLICATIONS

So, without the right set of skills for academia, I decided to change tactics again. Clearly academia was flooded with skilled and experienced scientists, so I focused on industry applications. The major barrier for job applications in this area turned out to be recruitment agents which many companies insist on using. Through a mixture of incompetence, and simple refusal to consider any application without GMP written on it I made almost no progress while “working” with recruitment agents. The best success I’ve had with industry applications has been direct applications to the  company itself, even when they are not advertising positions. I’ve received emails from the owners of smaller companies thanking me for my interest, I’ve made new contacts which may lead to work years down the line, and importantly they now know I exist, and I have skills that are useful to them.

PLAN Z - BACK TO EDUCATION...SORT OF

After nine months of applications without any success I decided to take advantage of the new government sponsored upskilling programmes run for science graduates to allow employment in the pharmaceutical manufacturing sector. Despite the government parading the term “knowledge based economy” at every opportunity, this is not backed up by private or public investment in research facilities here. Instead Ireland is used as a manufacturing hub requiring specific skills which can only be obtained through years of industry experience. In the hope of acquiring some of these skills I joined, and subsequently left a state sponsored course designed to ease the transition between academia and industry. Overall, things were beginning to feel a bit like this.

After attending the first lecture I realised I could teach the material, so I offered my services for free. I would get good lecturing experience, reduce their work load at the same time, as well as possibly leave myself in a good position for getting paid work down the line. This looked like it might go somewhere, but it turns out there are bureaucratic difficulties in turning up somewhere to work for free. Everyone involved wanted it to happen, but it couldn’t be done. Least helpful of all were the department of social welfare. Since I was on social welfare payments it would be illegal for me to volunteer for anything that was not on their list. University lecturing was not on their list, neither was laboratory work.

JOBS-BRIDGE

While attending a second state sponsored course I was called for interview for an internship I had applied for months previously. It was out of my field of expertise, but since the idea of jobs-bridge was to allow inexperienced graduates to upskill I was hopeful something would come of it, and amazingly it did. I was offered the position, a nine month contract performing research in analytical chemistry, where I would gain hands on experience with relevant techniques. I was happy to accept accept the position, 18 months after I first started applying for jobs.

THE HAPPY ENDING

My current situation is that I’m employed full time on a 5 year contract. I’m gaining relevant experience in a regulated industry setting while performing research that I find fascinating, and challenging in equal measure. For me, the jobs-bridge programme was critical to my getting a foot in the door. It allowed my employer to take a chance on me, set up an experimental research project at low cost until such time as they were in a position to hire me.

MY ADVICE

From December 2010, to September 2012 I applied for over 100 jobs mostly within Ireland and the UK, and was called for interview on 10 occasions. As a newly graduated Ph.D. I found it impossible to get my foot in the door, and for anyone to take me seriously. The tide is beginning to change now as experienced people are being snapped up, and companies are becoming more flexible on their requirements. But I don’t envy anyone looking for work over the next few years.

The best piece of advice I can give here is where at all possible bypass the recruitment agents completely. For the most part they are not scientifically literate, and they will have almost no understanding of what the job entails. Secondly, persist! Keep applying, and where possible get in touch with the company directly. Finally, join LinkedIn, and use it. Posting answers to questions on its forums is a great way to make new contacts and establish a name for yourself as someone who knows their subject matter, but also as someone that cares about their work, and act collaboratively to solve problems. Finally, get that first few months experience if you can. It might mean working for free, but it won’t be forever.

Do You Mendeley? - My Experience of a Stress Free Reference Management Tool

BACKGROUND

As an experimental biochemist embedded in a largely computational research group I was lucky enough to be exposed to some clever software tools that simplify everyday tasks such as primer design, DNA sequencing, homology modelling, and viewing protein structures. However I noticed my peers were still performing many tedious tasks by hand, or using some really terrible software. The best example of this was reference management, where Endnote was essentially ubiquitous, but everyone had problems with it. However, there is a better way. Mendeley is a free reference management tool that integrates seamlessly with MS Word, and Open Office. The developers of Mendeley have an excellent website with easy to follow tutorials on the main features, see here, but nothing beats the experiences of someone who uses it on a daily basis.

WHAT IS MENDELEY?

Essentially, Mendeley is iTunes for your research papers. Its allows for easy uploading, storage, and retrieval of your papers from multiple computers, in multiple formats. In addition, it automatically generates a copy of all your documents on the cloud, thanks to the free 500Mb of storage space they provide for every user. Here is what it looks like when you have built your library. 

You can see it's very well laid out. The main screen is your selection of research papers, with all the useful details listed such as title, authors, year of publication, and journal. Just having all your research papers like this makes a huge difference to how you find and use them. Mendeley is packed full of useful features, but after using this software for over two years the main features I think people will be interested in are as follows,

• cataloguing of all of your research papers visible through one portal
• super-fast library searching
• sending and receiving documents to/from other Mendeley users
• access the original website from which the article was downloaded
• digital annotation and highlighting of articles/sections of articles
• the ability to access your library from any online computer

CREATING YOUR LIBRARY

Creating your library is straightforward. I found the best way was to simply select the “Watch Folder” option from the add files menu in the main toolbar, and browse to the folder which contains your documents of interest. They can be pdf or word documents. Mendeley will now proceed to add each document to the library, scanning each for useful details such the title, the authors, the journal it was published in. In addition, any documents subsequently added to the folder will now automatically be visible in Mendeley. The documents do not need to be labelled logically for Mendeley to populate the metadata for each article. This is akin to letting iTunes fetch the details of a particular track for you, so that you have the correct album art, singer, album name etc. However, Mendeley does not always get this right, so some manual manipulation may be required to clean up the data. I consider this a small price to pay considering the benefits granted by the rest of the functions. Once you have your documents imported I recommend using the synchronisation functionality, this uploads everything to the cloud storage they provide, allowing you to access it from any computer with an internet connection.

SEARCHING YOUR LIBRARY

Once you have imported your documents the first thing you’ll notice is that double clicking on any one of the articles beings you to a full version of the document. This is fully searchable via the toolbar on the top right. It might not seem like a major feature, but when you’re trying to remember where you came across the evidence for that statement in your thesis it’s an extremely valuable and saving feature. In addition, your whole library is searchable, so you can search for authors names, or journal name, or just individual terms you are interested in. It’s happened to me before that I couldn’t remember the author, but I could remember a particular term used with the article, a few keystrokes quickly narrows down the list of possible suspects. It’s worth noting, the more effort you put into having the correct details for each article the better the results of any search will be. If you’re slightly OCD like me you’ll actually get enjoyment out of making sure everything is correct, and welcome the distraction from writing your thesis.

SENDING/RECEIVING ARTICLES

How much you use this feature depends on how collaborative your research group is, and how many other people you can convince to use Mendeley. Essentially it allows you to select any of journal articles from your library and send them to any other Mendeley user that you have invited to join Mendeley. It’s actually much quicker than email, and the document is automatically integrated to your existing library, including any notes, and annotation made by the previous “owner”. The recipient does not have to have a subscription to the online publisher of that article, so it’s an excellent way to share papers among less privileged colleagues.

ACCESS TO ORIGINAL URL

This is perhaps one of my favourite features in Mendely. It very common for the research paper you are reading to cite other articles of interest. Tracking down references can be extremely time- consuming (read pain in the ass!) depending on how the original paper referenced them. The easiest way by far is to go to the URL of the original paper, and hope that they have supplied there list of references as hyperlinks. This would allow you to get all their references relatively quickly. However, even this means you still have search for the original paper in Google Scholar, or PubMed, Mendeley can by-pass all of that time consuming nonsense by providing the URL of the source article you are reading in the right-hand toolbar. Think about what this means now. With the URL provided to you all you have to do is click on the link and you are on the correct webpage for that article! From here you can go straight to the reference section of the look for hyperlinks. It’s an extremely fast and very effective way to navigate from source to source with no typing involved. 

DIGITAL ANNOTATION AND HIGHLIGHTING

A relatively minor, but useful feature of Mendeley is that individual documents can be have “sticky notes” attached to them, essentially a collapsible text box which you can place anywhere. Generally useful for making quick notes of questions, or thoughts as you read the paper. It’s also possible to make more detailed notes in the toolbar on the right hand side, this is a better option in my opinion, since these notes are searchable, so you can actually pick out a paper based on the contents of the notes you made as you were reading it.

ACCESS, ANYTIME, ANYWHERE

Provided you have synchronised your library and you have downloaded Mendeley you will have access to your library from any computer with an internet connection. So, for example, I used to do the majority of my thesis writing in my University. But occasionally I would work from home. For me this meant I lost my access rights to the journals that supplied all those nice papers I needed. So. on these occasions I would make sure to dump any relevant research paper I could into Mendeley nd syncronise it before leaving for home. Once home, Mendeley allowed me to continue reading and inserting citations to my thesis as if I had university access. But if I ever needed something I could always get it send to me from someone who also had that document in their library. This allowed for seamless integration between multiple computers. In fact during the writing on my thesis I went through three laptops and two desktops, but it was never a problem, my library was always on the cloud, and between Dropbox and Mendeley I was back writing from where I left off within 20mins of switching to an entirely new computer I had never used before. Think about that for a moment, normally a computer failing is a massive problem mid-thesis write up. But Mendeley and Dropbox together meant I never had a single problem I could not recover from quickly. 

THE CONCLUSION

In short, I can’t recommend this software highly enough. It's fantastic. It’s intuitive, and actually fun to use. On the one occasion I had a technical issue it was resolved within 24 hours, with follow up from the support team to make sure I had what I needed. Bear in mind, this is free software, and the support they offer is far superior than anything I’ve experienced with Dell, or Microsoft. Download it, play with it, and enjoy stress free referencing! Do it now! :)

Drugs of Abuse - Amphetamines, Ecstasy and Cathinones.

BACKGROUND

People have been using psychoactive drugs for pleasure for thousands of years. From the Areca nut used as a mild stimulant in Timor over 13,000 years ago, to the coca leave cultivated in South America 5,000 years ago it seems the human brain craves stimulation, and consequently, new and interesting stimulants. Modern day humans are no exception. We're all used to hearing news stories about heroin, cocaine, ecstasy and LSD, but lately there has been an explosion in both the number and types of new drugs available.

WHAT'S THE PROBLEM?

Regulatory authorities are struggling to keep up with the number of new "illegal" drugs on the market. I say "illegal" simply because it's not clear how these compounds should be classified. The complexity in the law governing the use of drugs arises from the subtleties of the chemistry at the atom level. For instance, for any given compound, legal or not, a difference of a single atom anywhere in the structure results in a compound which is completely unique. There may not be anything known about this novel compound, and consequently, there is no legislation governing it's use.

For example, lets examine the chemical composition of two drugs, one legal decongestant called pseudoephedrine, and one illegal drug called methamphetamine, (crystal meth). Pseudoephedrine is available from pharmacies as an over the counter medication. It's the active ingredient in Sudafed for example. Structurally, pseudoephedrine looks very similar to methamphetamine, see the picture below. In fact there are just two atoms in the difference.

If nothing was known about pseudoephedrine a toxicologist looking at it for the first time might expect it to have a similar effect to methamphetamine, that is, stimulatory, promoting alertness, and increasing reaction time. But it's very difficult to judge the effect of those two extra atoms. The additional (-OH) present on pseudoephedrine could make it more or less potent as a stimulant. Perhaps it's metabolised more quickly by the body? Perhaps it's more soluble in the blood now? Perhaps it has a harder time getting into the brain? A good toxicologist can make good predictions, but they are just that. Until detailed studies are performed it's really not known how a particular drug will behave.

This is the root of the difficultly for legislators. If there was a decision to make pseudoephedrine illegal this might go some way to curbing it's use. However, a single atom change to it's structure results in an entirely new compound. It's perfectly possible that nothing is known about the physiological effects of this compound, beyond it's ability to produce a chemical high. This is exactly what happened with ecstasy (MDMA) production recently. One of the precursor ingredients for MDMA was made illegal. The idea was to make it more difficult to manufacture MDMA and ultimately make people safer.

However, far from making people safer this change in legislation resulted in the rise of a new ecstasy like compound called PMMA. Both MDMA and PMMA have similar effects, but the effects of PMMA come on much more slowly. Thinking the drugs weren't working, or that they had taken a really low dose, regular MDMA users would take more and more PMMA waiting for the effects to kick in. Needless to say, when the effects did kick in things got serious. Very quickly after the emergence of PMMA there were media reports of overdoses across Ireland and the UK. Sadly, this is a stark example of legislation that was introduced to prevent harm actually causing more harm than good.

Fuck it, lets just make everything legal!

MEDIA ATTENTION ON DRUGS

2014 saw the introduction of over 100 new synthetic drugs of abuse in Europe alone. With such a wide array of new street drugs it's no longer surprising to encounter a news story including the name of a drugs most of us have never heard before. For example, this was a recent headline in America. 

The drug being referred to here is called alpha-pyrrolidinopentiophenone, or alpha-PVP for short, street name Flakka, or Gravel. But what is this drug, and where did it come from?

ALPHA-PVP

Alph-PVP is a synthetic stimulant which belongs to a class of drugs called cathinones. Cathinone itself is naturally occurring, being found in the plant called Khat. The leaves of this plant can be chewed to produce mild stimulation. The structure of cathinone is shown below, along with the khat plant it's found in. Interestingly you can see it looks a little bit like methamphetamine, so it's not too surprising to learn that this drug is a stimulant. It also induces paranoid delusions, with users reportedly fearing for their lives after hallucinating gangs of people chasing them down!

The chemical structure of cathinone (left) and the plant which makes it Catha edulis, (right).

At this point it's important to point out here that whether or not a compound is synthetic has no bearing on its safety or toxicity. There are many synthetic compounds which are safe, and many natural compounds that are dangerous. In the case of PVP, the naturally occurring cathinone molecule was modified by a chemist to produce a novel synthetic compound. This is the case with all synthetic cathinones which include mephedrone (M-CAT, Meow, Meow), and MDPV, (Bath Salts), both of which get sporadic media attention as a result of fatal or near fatal overdoses. The structures of these compounds are shown below. If you know a little chemistry you can see they look a little like the structure of cathinone, shown above. Variants of cathinone are continously made to circumvent the laws which ban them. Thus, it is often not illegal to manufacture or sell these compounds.

You could argue that all that's required for legislators to get a handle on this is an outright ban of all cathinone compounds. The problem with that idea is that some cathinones are actually medicinal, and are used as antidepressants for example. Making all cathinones illegal immediately makes research into these drugs more difficult. Any research laboratory wanting to investigate these compounds would now need to apply for a licence to have them on the premises. This is a bureaucratic nightmare, enough to put off many research scientists who simply don't have the knowledge or the resources to work in such a regulated environment. Regardless of whether or not you think this is a poor attitude for a scientist to take, the reality is more barriers to research means less research is done.

Those using synthetic cathinones recreationally can be often experience far more intense "highs" than expected. Part of the problem with illegal or unregulated drug manufacture is that the contents are not tightly controlled, so the potency between batches is extremely variable. By contrast, any drug manufactured legally by a pharmaceutical company must undergo a multitude of quality control (QC) checks to ensure purity before being distributed.

SUMMARY

New drugs are being manufactured all the time. Legislation designed to protect the population from the risks and harms of drug use have actually compounded the problem resulting in deaths from the distribution of PMMA marketed as Ecstasy (MDMA). At the same time, there is increase in the number of synthetic cathinones, producing powerful psychoactive stimulants. Almost nothing is known about the physiological effects and safety of these stimulants. By contrast, the physiological effects of compounds such as amphetamine, methamphetamine and cathinone itself, are known and documented in detail. I hope this segment has given some insight into the science behind the news headlines, and the difficulties faced by regulators and scientists working in this area.

As always, comments are welcome. 

USEFUL INFORMATION

• Database on new psychoactive drugs in Europe
• Guardian Science Podcast on PMMA
• FOX news article on Alpha-PVP
• Information on Synthetic Cathinones.
• Irish Times News Story on PMMA Deaths
• Review of Flakka

Universal Blood Cells.

BACKGROUND

Some time ago, while making my way home from college, I was listening to an episode of a podcast called Science Friday. It was dark and cold outside and I was keen to get home, eat and be warm, so it's safe to say my mind was not on the material at hand. Even so, what I heard blew my mind, it seemed too simple to be true, and yet it made perfect sense. I was immediately annoyed I hadn't come up with the idea myself. The idea? Universal blood cells. I'm going to keep you in suspense as to what that means while I explain more about blood in general.

BLOOD

Blood is composed of red blood cells (also referred to as RBCs, or erythrocytes), white blood cells (also referred to as WBCs, or leukocytes), and platelets. This varied composition allows it to perform a myriad of essential functions. For example, RBCs are responsible for the transport of oxygen, (O₂), from the lungs to every other organ and cell in the body. In addition, they also exchange this oxygen for a waste product of glucose metabolism, carbon dioxide (CO₂), and return it to the lungs to be expelled. Therefore there is a constant exchange of CO₂ for O₂ going on in the lungs, with blood being continually circulated around the body to remove/supply both. WBCs are a much more complicated group. There are five different subtypes of WBCs, but together they form part of our immune system, allowing us to fend of biological attacks from viruses and bacteria. Finally, plateletes are responsible for some housekeeping activities such as blood clotting, maintenance of blood vessel lining, and digestion of harmful bacteria.

The composition of blood, image taken at http://www.myvmc.com/anatomy/blood-function-and-composition/

In addition to all of the above functions blood also has the added function of regulating pH, regulating body temperature, and generally acting as a delivery mechanism throughout the body for the supply of nutrients such as glucose, amino acids, lipids, vitamins and salts. So, blood is important, and it's able to perform all of these functions because of the complex composition of RBCs, WBCs, and platelets. 

CELL BIOLOGY 101

Cells are the basic unit of life, by which I mean all living things are composed of either a single cell, or many cells, termed unicellular or multicellular respectively. But cells themselves are incredibly complex, and in the same way that we have specific organs performing specific tasks for us, our cells have tiny structures inside them called organelles performing specific tasks for them. This could be the production of protein, or conversion of sugars into cellular energy. But the complexity of a cell continues to the outside. All animal cells have a fatty cell membrane called a phospholipid bilayer separating it from the outside world. This lipid bilayer is protective, but also functional. It's scattered with protein and sugar molecules that allow it to regulate transport in/out of the cell, and generally communicate with other cells around it. Sugar and proteins sometimes combine to form what is called a glycoproteins, and these are important molecules.

BLOOD GROUPS

Most people will have heard the term blood group. But what does it actually mean? Well, there are four different blood groups called group A, B, AB, and O. It turns out that the glycoprotein surface is what determines your blood group. There are many different types of sugars, and they have names like glucose, fructose, and sucrose. In the image below "GAL", "GAL-Nac" and "FUC" are sugars called galactose, N-acetylgalatosamine and Fucose respectively. You can see how all three blood groups share the same GAL-GALNAc-GAL backbone, but differ in their terminal regions. For example, blood group A has an additional Gal-Nac sugar molecule compared to blood group O, while blood group B has an additional GAL sugar molecule compared to blood group O. Blood group A is further subdivided with blood group A₁ and A₂ being the most common.

Schematic of the A, B, and O blood groups. The red oval represents the red blood cell. The coloured hexagons represent the different sugars that attach to the blood cells to make its blood group.

MEDICAL RELEVANCE

Blood groups are extremely important for blood transfusions. The blood groups between donor and recipient must match otherwise the body will reject it. All blood groups can donate to themselves, so group A is compatible with A etc. However, blood group A is not compatible with blood group B, and the reverse is also true, group B is not compatible with group A. Group AB cannot be given to group A, or B. Group O however can be given to every blood type, which makes it extremely valuable. The compatibility of different blood groups can be summarised in the diagram below. Red arrows indicate blood groups which cannot be exchanged.

The compatibility of each of the blood groups, red arrows indicate blood groups which cannot be exchanged.

Invasive surgery requires blood transfusion while the operation is being performed, so if there's no time to test the blood type of your patient then you know it's safe transfuse blood O without resulting in any additional complications. Transfusing the wrong blood will lead to activation of the immune system, destruction of the new blood cells which ultimately can result in death.

UNIVERSAL BLOOD CELLS

The idea I ended up stumbling across that night while listening to my podcast was to generate blood group O cells from bags of group A, B, and AB blood. That is, the ability to take any blood type and modify it so that it's capable of being transfused without any immune response in the patient. This idea, if feasible, would make all of the current blood stocks capable of being donated to any patient! That's pretty amazing!

HOW DOES IT WORK?

The basic science behind this is involves the application of a well established biochemical technique called enzymatic hydrolysis. Enzymes are protein molecules which have the ability to add or remove chemical components to specific molecules, I've mentioned them before in a previous blogpost so I'll skip over a detailed explanation  here. There are pre-existing enzymes in nature which will selectively remove the N-acetylgalatosamine and Frucose sugars from blood cells. Interestingly, the first attempts were with an enzyme found in coffee beans, but subsequent attempts using different versions of the same enzyme resulted in much better efficiency. The image below shows how these sugars actually look and demonstrates how the conversion of group A or B to group O involves the removal of just one molecule of sugar. The sugar removed in each case is highlighted by a coloured star.

Conversion of blood groups A and B to group O. Image adapted and modified from the original research paper on this topic, "Bacterial Glycosidases for the production of universal blood cells" 

There are two enzymes used for this, once called α-N-acetylgalactosaminidase for removing the sugars associated with blood group A, and a second called α-galactosidase for removal of sugars associated with blood group B. The actions of enzymes result in blood group O cells. The structure of α-N-acetylgalactosaminidase enzyme bound to a single sugar molecule is shown below. On the left is an image of the whole enzyme/sugar complex (shown in grey, red and blue), with the sugar shown in purple. The image on the right is the same enzyme/sugar complex zoomed in to show the the complex in more detail. Enzyme often have small clefts or holes in their structure into which their substrates fit. All the chemistry associated with the removal of this sugar molecule happens in and around this small cleft area, called the active site.

The α-N-acetylgalactosaminidase enzyme, bound to a sugar residue. Image made using YASARA, and PDB ID 2IXA.

The α-N-acetylgalactosaminidase enzyme, bound to a sugar residue. Image made using YASARA, and PDB ID 2IXA. 

WHY THIS IDEA IS COOL

Biological material like blood is sensitive to large changes in pH, or temperature. In addition, it's important to keep it free from any external contamination. Biochemists are familiar with this so we add reagents to control the pH, we keep solutions cold, because it helps preserve the integrity, and slow bacterial degradation of the components and we often work in sterile conditions to prevent any contamination. This is time consuming and expensive. But one of the cool things about the procedure used to make this blood is that it is relatively easy. There are no difficult or expensive conditions required. The enzymes required were simply added to a 200mL volume of blood which had been washed with buffer solution, the solution was then mixed gently for 1 hour at room temperature, after this the blood was washed with a salty solution to remove the enzymes. In addition, even though there are different enzymes responsible for converting blood groups A and B it was possible to simply add both enzymes to a single unit of AB blood and let both of them operate together to produce a unit of blood group O.

THE DISADVANTAGES

There are some disadvantages with the enzymatic hydrolysis of blood cells. The research group responsible for demonstrating this modification of blood cells has shown it works on a small scale, but for this to be really useful it would need to be able to convert thousands of units of blood every week. Such large scale conversion would require large quantities of the enzymes used. Specifically, for the conversion of 1 unit of blood group A1 to blood group O the researchers mention they used 60mg of enzyme. Recently the Irish Blood Transfusion Service (IBTS) advertised they needed 1,500 units of group O blood each week. To convert 1,500 units of blood would therefore require 90,000mg (90g) of enzyme every week.

It's a little difficult to put this in perspective, but I used to make enzymes as part of my Ph.D work. This is done via the genetic modification of microorganisms, bacteria or yeast cells for example, which are then grown in what is called a bioreactor, or fermentation vessel. Typical yields of protein are pretty low, in the order of 100mg/L of cell culture material. So the ability to make 90g of enzyme every week is demanding, and expensive, but by no means impossible. Biotechnology companies are used to this problem, and utilise large scale bioreactors, in the order of 20,000L, to mass produce therapeutic proteins for other medical reasons. This is currently being done for diseases like diabetes, where insulin is required in large quantities for worldwide supply, so there's no technological reason why this could not be done for these enzymes.

SUMMARY

Blood donations are always needed, and in particular blood group O is in high demand because it is accepted by any blood group. Supply is always going to be restricted due to legitimate medical reasons such as disease, so anything that can be done to ease the strain on supply is definitely worth considering. The research presented here is simple, but clever, and uses well established biochemistry techniques. It might not be feasible to produce quantities of enzyme that are required, but there's a few more tricks that biochemists can perform the make it better. We can modify the protein using genetic engineering, to make it behave more efficiently, removing the sugar molecules more quickly. We can also try different ways to manufacture the enzyme which might improve the quantity we obtain. In short, this is a fantastic idea, and worth pursuing further, and I'm still annoyed I didn't think of it first!

How Does Penicillin Work?

ANTIBIOTICS

The first antibiotic, penicillin, was discovered serendipitously in 1928 by Alexander Fleming. A medic by training Fleming went on to specialise in bacteriology before leaving his comfortable lecturing position for the trenches of World War I. He served as a medic in French field hospitals on the western front. There's no doubt that during his military service Fleming was exposed to the horrific toll that bacterial infection caused wounded troops. Many amputees died from non-life threatening surgery due to infections obtained in unsanitary field hospitals. But the discovery of penicillin revolutionised surgery, allowing patients to recover from infections that could otherwise kill them.

Alexander Fleming, perhaps not the happiest scientist there ever was. 

So effective was this wonder drug that Fleming was awarded the Nobel prize for Medicine in 1945. By this point, penicillin had saved thousands of lives both on and off the battlefield.

So how does Penicillin work? Well, to understand that one needs to understand the basics of cell biology. Cell biology studies with what cells are made of, and how they operate. A detailed understanding of cell biology is beyond the scope of this post, but it is useful to understand bacteria in the context of other forms of life. 

TYPES OF LIFE

It might seem surprising, but every living thing on the planet can be categorised into just there different branches on the complex tree life. These branches of life are called Prokaryotes, Eukaryotes, and Archaea. In addition there are also viruses. Viruses are often difficult to introduce when discussing simple life-forms because while they are much more simple than a bacteria cell, they are not always considered living cells. They have many of the characteristics of life, movement, sensitivity to their surroundings and so on, but unlike living cells they are unable to reproduce without a host cell. That is, they rely on infecting a bacteria or human cell to make more copies of themselves. For this reason, viruses are often considered nothing more than assembles of biomolecules, albeit, very interesting and often dangerous assemblies of biomolecules.

THE ARCHAEA

The Archaea branch of life contains the simpler organisms, the early forms of bacterial life on earth. They are single celled with an amazing ability to survive and adapt, often living in environments that we would consider hostile. For example, there are some Archaea bacteria that live in the very darkest depths of the ocean, in close proximity to hydrothermal vents. These living conditions contain extreme pressures and temperatures and there no sunlight. However, this proves to be no obstacle to these hardy organisms who thrive on the constant supply of noxious chemicals released from deep below the surface of the earth. 

THE PROKARYOTES

Like the Archaea, these are simple, unicellular organisms, but they tend to live in less hostile environments. These are the bacteria you are more likely to have heard of. The E.coli bacteria associated with food poisoning for example, or MRSA infections commonly contracted in hospitals. Prokaryotes are tough, adaptable, and capable of reproducing quickly making them potentially very dangerous. However not all of them cause disease in human (a quality known as pathogenicity). Some are actually beneficial to us, bacteria in our intestine actually help us digest food we eat, and produce vitamins for us in return.

THE EUKARYOTES

Finally, the eukaryotes. These are the most complicated organisms, and include some unicellular life such as yeast cells, but also the more complicated multicellular organisms. This includes everything from sponges to worms to humans. The individual cells that make up a human are much more complicated than an individual bacterial cell. This complexity comes at a price, namely the speed at which a human cell can make more of itself. Bacteria are very quick to reproduce but human cells, by comparison, are slow but make a more faithful copy of themselves. 

THE ANATOMY OF BACTERIAL CELLS
Bacteria themselves are incredibly interesting lifeforms. Although more simple than us they are  still very complex. They consist of a bunch of cell organelles, and some DNA wrapped up in a fatty skin called the cell membrane. Surrounding this cell membrane is a tougher shell called the cell wall. The cell wall is made of a tough material called peptidoglycan, and offers the bacteria some protection from the outside world. You can think if it as multiple layers of wire mesh; rigid, strong, but also flexible.

The anatomy of a bacterial cell. The yellow "skin" on the outside represents the cell membrane, and the cell wall. 

This peptidoglycan mesh is a composite of sugars and amino acids. The sugar components have the unwieldy name of N-acetylglucosamine, and N-acetylmuramic acid so for ease, biologists abbreviate these to simply NAG and NAM. NAG and NAM sugars are joined together in a chain, and individual chains become cross-linked with small protein molecules for extra strength and rigidity. As with many processes in biology the formation of a bacterial cell wall is facilitated by an enzyme, in this case, an enzyme called transpeptidase.

This image shows the function of the transpeptidase enzyme in making bacterial cell walls. The red and orange hexagons represent the individual NAG and NAM sugars that combine in long chains. The chains have small pieces of sticky protein (peptides)  hanging from every NAM molecule. The transpeptidase stitches each NAG-NAM chain together by fusing the peptides molecules together. These fused chains are the basic structure of a bacterial cell wall. 

Bacteria are constantly making and degrading their peptidoglycan cell walls during the process of cell division. It's a necessary part of how the divide and make more of themselves. Without the ability to make and repair their cell walls bacteria become flooded with water from outside the cell, and burst. A process called cytolysis. Therefore, the transpeptidase enzyme is essential for the survival of bacterial cells. Some antibiotics work by inhibiting the action of this essential enzyme. But how?

THE STRUCTURE AND FUNCTION OF ANTIBIOTICS
There are many different types of antibiotics, and they can be classified on the basis of their chemical structure, mode of action, or spectrum of action. As mentioned, Penicillin works by inhibiting bacterial cell wall synthesis, but other antibiotics work in different ways. What is it about penicillin that makes it work the way it does? Well, like a lot of biochemistry, it all comes down to to the atomic structure of the penicillin molecule. Fleming did not know this at the time of his discovery, but penicillin actually looks very like the peptide molecules used to strap the peptidoglycan chains together.

So, when we take penicillin to treat a bacterial infection we are presenting the bacterial transpeptidase enzyme with a choice. The enzyme can either, grab hold of the peptide molecule (D-Ala-D-Ala) like it's supposed to, or it can grab a molecule of penicillin. If it grabs a molecule of D-Ala-D-Ala then everything goes to plan, at least as far as the bacteria are concerned. Cell wall biosynthesis occurs normally, and the bacteria happily go about reproducing. However, if the transpeptidase enzyme grabs a molecule of penicillin instead of D-Ala-D-Ala, then the bacteria are in trouble. Penicillin will bind strongly to transpeptidase enzyme, effectively gumming up the works. We now have a situation much more like the image shown below.

Here, the penicillin molecule is represented as the yellow and black circle, jammed in the mechanism of the transpeptidase enzyme.

Here, the penicillin molecule is represented as the yellow and black circle, jammed in the mechanism of the transpeptidase enzyme. With penicillin gumming up the works it is not possible for transpeptidase to do it's job. The more penicillin we take the more this situation occurs, making it very difficult for the bacteria to reproduce. This mechanism of actions applies only to penicillin and antibiotics that look like penicillin such as amoxicillin. Different antibiotics work in slightly different ways, targeting different proteins that are important for bacterial cell survival.

ANTIBIOTIC RESISTANCE
Antibiotic resistance is becoming an increasing problem. It refers to the ability of some bacteria to keep reproducing despite the presence of antibiotics designed to kill them. So, how have these crafty bacteria overcome our sophisticated chemical weapons? The answer is evolution. Every generation of bacteria results in a slightly new organism. It's still a bacteria, but it's ever so slightly different from the "parent" that made it. Sometimes these differences are enough to result in interesting properties such as antibiotic resistance.

Antibiotic resistance stems from an overuse of antibiotics in medicine. This could be over-prescription by doctors, or people administering for diseases not associated with bacteria, such as colds, or flu, caused by viruses.  For any given infected individual it is unlikely that a single dose of antibiotics will wipe out every single bacterial cell in the body. Any cells that are left will produce offspring which become resistant to their hostile environment, and thrive in their new competition free zone. Next time these bacteria encounter this antibiotic they have already adapted to it, and produce their own chemical weapons to destroy ours.

CONCLUSION
So, there you have it. Penicillin works by preventing the construction of bacterial cell walls, causing bacteria to explode via an intake of water. Penicillin is just one of many types of antibiotic, which can produce their effects in different ways. Bacteria are adapting to these chemical weapons by producing chemical weapons of their own, destroying of the antibiotics before they can take effect. This has resulted in an literal arms race between us and the bacteria, but we are losing. The result is multidrug resistant bacteria such as MRSA which is having a pronounced effect on hospital patients worldwide. If we are to win this arms race we need think differently, and stop relying on brute force approaches.