Productivity…

Productivity (Copyright Jorge @ phdcomics.com)

THE thing about being a practising scientist working in academia is that when such a practising scientist decides they want to write more about science in general, they remember that academia is a toxic gas that expands to fill all available space.

We might hope for reprieve from standing at the bench, just a small amount of time to get a handle on our writing, a quick moment to imbibe some of the multiple streams of information from emails, journal table of contents, RSS feeds; alas, the moment a window opens, it is filled with responsibility. This may come in the form of the help you promised someone when you next got a chance; or hunting down an expensive enzyme in neighbouring labs, of which you require a mere fraction of a unit for a throw-away experiment; it could be trying to find a journal article with some essential information, rather than one that is actually interesting. Alternatively, you may just sit and stare into space, your brain already so depleted of sugar that you are protocolling on auto-pilot.

Having filled your day with preparations for experiments, and the remaining 5% of it getting to finally do the experiments, you turn your attention to your student, who is working on a completely different project, with its own set of unique and inconvenient problems, and for which you must but don’t have answers.

Having finally left the lab, if you’re lucky, you’ll manage to get home in time to cook some award winningly simple food (credit us with some respect, some of us do cook from scratch), which is invariably eaten in front of the computer while you finally get to sift through the now ridiculously over-burgeoning information stream, which now includes – lucky me – about a million twitter entries and their links.

Ultimately, if you’re not ready to go by 2 am, you have two choices: either spiral into pit of information overload, eyes glazing over as the numerous ideas that pop into your head leave just as fleeting and unformed as they arrived; or sleep.

There are of course some researchers out there who do manage overwhelmingly with both their professional and private pursuits, hell, I even manage it myself sometimes. But right now, I need a week’s worth of sleep.

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Writing time…

So the university has afforded me some free time for the next five days, which gives me the perfect opportunity to get caught up on some of the science blogging I’ve been planning. In the next few days I will be posting some pictures and video that fall into the broad category, ‘Life in the lab’. In this I will be discussing topics, in no particular order, such as:

‘I’m just running a gel…’, – what does this line, often used by lab scientists, actually mean?

‘Using biology as a scaffold for building nano-electronic circuits…’ – this is some of the research I am involved in.

‘Toy’s for science boys (and girls)…’ – Yes, there are geeky tool kits (I call them toys) that we use in molecular biology. Most people won’t know the point of using them, let alone that they exist; I’ll attempt to explain why they’re cool.

Finally, I will be doing a research blog on ‘Targeted antibiotics…’ – new approaches to make antibiotics more useful, and that take out the ‘bad’ bugs, but leave the ‘good’.

Attention to detail…

[ratings]

Some MOST people would describe me as being a little moderately anally retentive; I have a rather punishing attention to detail, particularly so with the way I approach experiments. Something that really annoys me is when fellow scientists display a degree of slapdashness that borders on being negligent.

Many of us are publicly funded, and one of my aims in life is to communicate science to the public. I love science, both as a system within which I do research, and as a philosophy. If I am to wax lyrical about the rationality and worth of science, and the scientific method, to the public, and use it as a basis in arguments against irrationality, pseudo-science quackery and superstition, then I damned well better practice what I preach. As such I employ the skills and techniques I have learnt in a manner that takes account of these values; I design experiments with good controls, I vary the experimental variable whilst controlling the others. I use evidence-based methodologies that have been tried and tested, thus use minimal materials to achieve my ends in the minimal possible time.

It is not always possible to do this, especially in my current area where there are no protocols for what I’m doing as it’s never been done before. None the less, I form testable hypotheses, design experiments to test them and based upon the result, either modify, scrap or move on.

In your average science lab, based upon the very large number of science labs I have been to, I would have to say that the idea of sitting down and developing a testable hypothesis that makes predictions about outcomes, then designing experiments to test these is probably not what many researchers are doing. What they are doing is ham-fisting their way through protocols given to them by more senior players, which they follow blindly, often without knowing what each step in the protocol is doing at a physical level.

Many of these protocols have been adapted, cut-down and streamlined, which is often another way of describing that short-cuts, often rather slapdash ones, have been introduced. Now there is nothing wrong with this, per se, as long as the protocol is in the hands of a capable person who knows why the protocol has been revised in this way. But, the fact is you cannot instruct a junior member of research staff with protocols that have been cut-down in this way; the full anally-retentive protocol should be provided, or sought, and the researcher allowed to refine it once they’ve identified for themselves the pros and cons of keeping each step.

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A dichotomy of research…..

[ratings]

I AM a juggler by profession, but it is not balls that I juggle; instead, I juggle variables.

I currently work on basic technologies research. This does not mean to say that my research is basic, rather it means that the technologies that we are trying to develop are at a fundamental, or grass-roots, level. As such, some might call such research ground-breaking; though I hasten to add that this term is more considered in it’s metaphorical context. If any of you have ever had to dig in a new garden, or have led the way in deep snow on a mountain, then you’ll have some idea of what breaking new ground is all about. It is hard, unrelenting and there is no lateral movement, you either move forward into new ground, or you back-step until you get to base camp and set off in a new direction.

I am working on a biochemical reaction (a reaction involving biomolecules such as proteins and DNA) that has been shown to work in solution, in a tube. Other people have shown this, and I have shown it. However, interesting as this reaction is, we want to go further with it and have it work on a solid gold surface. Why? Well, ultimately we would like to be able to control the reaction by using an electric field, to turn it on or off, or better still control the precise level of its activity.

Having a biological system that works at the flick of a switch seems like a pretty cool idea, right? You’re sitting in a small, dusty village in central Africa or central South America. You’ve taken a load of blood and saliva samples that you intend to test for certain antibodies, or for the presence of current bacterial or viral diseases. It’s hot, there is no power and it took you a week of travel to get there. You are worried that your samples will degrade before you can get into a position to test them, and if you are especially well funded, you will have brought a whole portable lab with you, at great cost, and at great loss if it breaks on route.

What if, instead of the above hassle, you take out the small box you brought with you, in which there are several foil-wrapped packets containing plastic cassettes about the size of your thumb, but considerably flatter. What if you could inject the blood or saliva sample in at one end of the cassette, wait a minute and at the other end one of several LEDs light up. The combination of LEDs will tell you what the cassette has detected. Inside the cassette are small flow-channels that each contain different biomolecules that have all been painstakingly developed to function in this capacity. Simple, potentially very cheap, a laboratory on a chip.

Furthermore, you flick a switch on the cassette, which makes the juice from the small battery alternate from just powering the LEDs to instead put an electric field through the flow-cells; you can now conduct a second set of reactions using biomolecules that had been inactive until that point. TWO labs on a chip! Lab on a chip technology already exists, but there is much further for it to go, and this requires basic technologies research.

Ideally we would have a chip that could perform logic functions, so rather than it just detecting molecule A and it saying “hey man, you’ve got some molecule A here”, or likewise with molecule B; perhaps if molecule A and molecule B are both present, then this indicates something more serious, which is indicated by the presence of molecule C. Rather than you wasting time, and another chip, going back and testing the blood sample again for molecule C, the chip can detect both A AND B in combination, and in doing so will have activated another internal component that is able to then detect C. However, if the chip detects only B, NOT A, then this could indicate something else, so it triggers something that can detect this something else, perhaps molecule D. See? A logical chip.

Well, returning from the realms of near-future science fiction, in order to achieve any of the above in my basic technologies research, there are several variables we (meaning I) need to juggle, and this is where the fun pain starts:
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The perils of positivity….

IN science and medical publishing, everything is positive. Less than 4% of articles deal with negative results. There is a perception that negative results are non-results; only positive results are worth publishing. Why is it that showing that something does something is so much more important that showing that something doesn’t do something?

Obviously, I expect some common sense in this; I don’t very well expect that a paper should be published just because you have demonstrated that drinking water doesn’t cause sunburn, this would be a deeply unsurprising discovery. But what if it is a study that demonstrates that a particular drug doesn’t do what people expected it to do? What if it is a biotechnology that doesn’t work for a whole swathe of biological research?

Online science forums (or fora) are replete with anecdotal evidence describing how time, and time, and time again research scientists make the same mistakes, or encounter the same limitations, in particular techniques. This is because no-one ever publishes such limitations, or at least, not more than 4% of the time.

So what is the problem? Well, science is expensive. Very expensive. It is expensive in material cost, and it is expensive in research hours. To have discovered that you’ve wasted a year doing work that elsewhere in the world someone once wasted a similar amount of time doing, only, 3 years ago, is deeply frustrating.

In coffee breaks around the world, many scientists have discussed the idea of a Journal of Negative Results, a compendium that can be consulted at the outset of a research project to determine whether a technique or approach has already been taken toward a research problem, but has been found not to work. Sometimes such negative results a mentioned, but only in passing, and only after an alternative technique resulted in positive results, which resulted in the subsequent publication. They are rarely keyword searchable and thus inordinately difficult to find.

As I mentioned, science costs a lot of money, far more money than is necessary. This is largely because the money isn’t real, there is poor ownership of it, it is monopoly money. If it were coming out of our own pockets, we simply wouldn’t pay the price we do, we’d demand more competitive prices. Consumable companies are free to charge extortionate prices for items that they are producing by the million. I have tubes in my lab that cost £3.75 each; they can only be used once, and invariably one or two of them can be wasted due to one problem or another. Kits are all the rage in research; pre-fabricated methodologies with all the reagents and instructions one needs to perform a particular experiment. The reagents themselves cost practically nothing in most cases, yet the kits can cost anywhere between £300 – £1500, and in many circumstances, afford you between 5 – 20 experiments.

Now this combination of expensive research is part of what leads to negative results being unwanted. There’s no real money in debunking an idea, it must come along side a positive result if it is to come at all. In the pharmaceutical industry, it is part of the reason why any new drug being produced is just too much of an investment to allow to fail, so the pressure is on to ensure, by hook or by crook, that the drug is licensed. Ben Goldacre writes at length about this in his recent book, and blog of the same name, Bad Science; this is most definitely worth a read!

Expensive research also prevents investment into rarer diseases, or any medications that run the risk of having a short shelf-life. One class of drugs that have fallen foul of this economic equation are antibiotics, and this is a rather long pre-amble into what I wanted to say in this blog essay (or blessay, and Stephen Fry attests to horribly calling it).

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