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Biotech for all – taking science back to it’s roots?

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This morning I came across a very interesting TED talk by Ellen Jorgensen entitled “Biohacking — you can do it, too” (http://on.ted.com/gaqM). The basic premise is to make biotech accessible to all, by setting up community labs, where anyone can learn to genetically engineer an organism, or sequence a genome. This might seem like a very risky venture from an ethical point of view, but actually she makes a good argument for the project being at least as ethically sound than your average lab. With the worldwide community of ‘biohackers’ having agreed not only to abide by all local laws and regulations, but drawing up its own code of ethics.

So what potential does this movement have as a whole? One thing it’s unlikely to lead to is bioterrorism, an idea that the media like to infer when they report on the project. The biohacker labs don’t have access to pathogens, and it’s very difficult to make a harmless microbe into a malicious one without access to at least the protein coding DNA of a pathogen. Unfortunately, the example she gives of what biohacking *has* done is rather frivolous, with a story of how a German man identified the dog that had been fouling in his street by DNA testing. However, she does give other examples of how the labs could be used, from discovering your ancestry to creating a yeast biosensor. This rings of another biotech project called iGem (igem.org), where teams of undergraduate students work over the summer to create some sort of functional biotech (sensors are a popular option) from a list of ‘biological parts’.

image

The Cambridge 2010 iGem team made a range of colours of bioluminescent (glowing!) E.coli as part of their project.

My view is that Jorgensen’s biohacker project might actually have some potential to do great things. Professional scientists in the present day do important work, but are often limited by bureaucracy and funding issues – making it very difficult to do science for the sake of science. Every grant proposal has to have a clear benefit for humanity, or in the private sector for the company’s wallet, which isn’t really how science works. The scientists of times gone by were often rich and curious people, who made discoveries by tinkering and questioning the world around them, and even if they did have a particular aim in mind they weren’t constricted to that by the agendas of companies and funding bodies. Biohacking seems to bring the best of both worlds, a space with safety regulations and a moral code that allows anyone to do science for whatever off-the-wall or seemingly inconsequential project that takes their fancy – taking science back to the age of freedom and curiosity.

Insights into the beginnings of microbiology

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Pasteur Institute
Over the holidays I rediscovered a book I picked up in an antique shop a year or so ago called “Milestones in Microbiology”. I had assumed it was going to be a standard history book with lots of dates and names and events, but it turned out to be a collection of groundbreaking microbiology papers from the 16th century to the early 20th century – quite a special find for a microbiology student. Many of the papers included were written by familiar names such as Pasteur, Leeuwenhoek, Lister, Koch, Fleming and more, and the collection was compiled and translated by Thomas Brock (a familiar name to anyone who’s been set Brock’s Biology of Microorganisms as a first year text book!).

I’ve not yet read the whole collection, but having read the first few papers I’m very much sold. The early texts on the field of microbiology are not just intriguing but fairly accessible too. The style of writing is far less technical than today’s academic papers, as well as being in full prose (in those days journals didn’t have strict word limits). My favourite example of this so far is when Leeuwenhoek describes one of his test subjects as “a good fellow” a comment that would be branded unneccessary and completely aside from the point in today’s academic world!

It’s not often you get the chance to view groundbreaking scientific advances through the eyes of the scientists you get taught about in the textbooks. Reading the paper in which Leeuwenhoek first describes bacteria (or “little animals” as he calls them) feels like something of a privelege, as well as a trip back in time, so definately worth a read for anyone with an interest in the field. A more up to date version of the book seems to be available on Amazon or for University of Sheffield students there’s a few copies in Western Bank Library – enjoy!

On another note, if you’re interested in this sort of thing I’d also definately recommend a trip to the Pasteur museum in Paris. I visited it a few years ago whilst in Paris and like the papers mentioned above it’s a fascinating insight into the work of pioneering microbiologists. It’s a fairly understated part of the modern Pasteur Institute, with the museum situated in the building of the original Pasteur Institute. The museum contains plenty of scientific curiosities, such as Pasteur’s original experimental equipment, and documents his work from his early background in chemistry and stereoisomers up to his more famous vaccine and microbiological work. Finally on a less biological theme, the museum also contains Pasteur’s living quarters and crypt, which were also part of the original institute building!

 

 

Want to lie convincingly? Get practicing!

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Lying, the deliberate attempt to mislead someone, is a processes that we all engage in at some time or another. Indeed research has found that the average person lies at least once a day, suggesting that lying is a standard part of social interaction (1). Despite its common occurrence lying is not an automatic process. Instead it represents an advanced cognitive function; a skill that requires more basic cognitive abilities to be present before it can emerge. To lie an individual first needs to be able to appreciate the benefits of lying (e.g. a desire to increase social status) so that they have the motivation to behave deceitfully. Successful lying also requires ‘theory of mind’ or the ability to understand what another person knows. This is necessary so that the would-be liar can spot firstly the opportunity to lie, and secondly what sort of deception might be required to produce a successful lie. Finally lying also requires the ability to generate a plausible and coherent, but nonetheless fabricated description of an event. Given these prerequisites it is unlikely that we are ‘born liars’. Instead the ability to lie is believed to develop sometime between the ages of 2 and 4 (2). The fact that the ability to lie develops over time suggests that the our performance of the ‘skill’ of lying should be sensitive to practice. Do people who lie more often become better at it?

Lying is tiring!
Lying is considered more cognitively demanding that telling the truth due to the extra cognitive functions that need to be utilised to produce a lie. The idea that lying is cognitively demanding is supported both by behavioural data showing that deliberately producing a  misleading response takes longer, and is more prone to error, than producing a truthful response (3) and by neurological data showing that lying requires additional activity in the prefrontal areas of the brain when compared to truth telling (4). These observable differences between truth telling and lying allow a measure of ‘lying success’ to be created. For example a successful, or skilled liar, should be able to perform lies more quickly and accurately than a less successful liar, perhaps to the extent that there is no noticeable difference in performance between truth telling and lying in such individuals. Likewise, if the ability to lie is affected by practice, then practice should make lies appear more like the truth in terms of behavioural performance.

Practice makes perfect (but is this a lie)?
Despite the intuitive appeal of the idea that lying becomes easier with practice, much past research has failed to find an effect of practice on lying, either when measuring behavioural (3) or neuroimaging (5) markers of lying. Such results have led to the conclusion that lying may always be significantly more effortful than truth telling, no matter how practiced an individual is at deception.

A recent study (6) has re-examined this issue. They used a version of the ‘Sheffield Lie Test’ where participants are presented with a list of questions that require a yes/no response (e.g. ‘Did you buy chocolate today?’). The experiment involved three main phases. In the first, baseline phase, participants were required to respond truthfully to half the statements and to lie in response to the other half of the statements. In the middle, training phase, the statements were split into two groups. For a control group of statements the proportion that required a truthful response remained at 50% for all participants. For an experimental group of statements the proportion that required a truthful response was varied between participants. Participants either had to lie in response to 25%, 50% or 75% of these statements, thus giving the participants differing levels of ‘practice’ at lying. The final, test phase, was a repeat of the baseline phase. This design allowed two research questions to be assessed. Firstly the researchers could identify whether practice at lying reduced the ‘lie effect’ on reaction time and error rate (e.g. the increased reaction time and error rate that occurs when a participant is required to lie, compared to when they are required to tell the truth). Secondly the researchers could identify whether any reduction in the lie effect applied just to the statements on which the groups had experienced differing practice levels, or whether it also generalised to those statements where all groups had the same level of practice.

The results revealed that practice did produce an improvement in the ability to lie during the period when the training was actually taking place, and that this improvement applied to both the control statements and the experimental statements. The participants who had to lie more demonstrated reduced error rates and reaction times compared to those who had to lie less during the training phase. However in the test phase this improvement was only maintained for the set of statements where the frequency of lying had been manipulated. The group who had practiced lying on 75% of the experimental statements were no faster or more accurate at lying on the control statements than the group who had to lie in response to just 25% of the experimental statements. These results suggest that practice can make you better at lying, but this improvement is only sustained over time for the specific lies that you have rehearsed.

Some lies may be better than others!
One important criticism of most studies on the effect of practice on lying is that they tend to use questions or tasks that require binary responses (i.e. yes/no questions). However in real life lying often involves the concoction of complex false narratives,a form of lying that is likely to be far more cognitively demanding than just saying ‘No’ in response to a question whose answer is ‘Yes’. Likewise the lies tested in laboratory studies tend to be rehearsed, or at least prepared lies. In contrast many real-life lies are concocted at short notice, with the deceptive narrative being constructed in ‘real-time’, whilst the person is in the process of lying. It is likely that the effect of training, and how that training generalises to other lies, will be different for these more advanced forms of lying than it is for the more simple types of lies that tend to be tested under laboratory conditions. Given this, if a psychologist tells you that we know for certain how practice impacts on the ability to deceive, you can be sure that they are lying!

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References

(1) DePaulo, B.M., Kashy, D.A., Kirkendol, S.E., Wyer, M.M. & Epstein, J.A. (1996) Lying in everyday life. Journal of Personality and Social Psychology, 70 (5) 979-995. http://smg.media.mit.edu/library/DePauloEtAl.LyingEverydayLife.pdf
(2) Ahern, E.C., Lyon, T.D. & Quas, J.A. (2011) Young Children’s Emerging Ability to Make False Statements. Developmental Psychology. 47 (1) 61-66. http://www.ncbi.nlm.nih.gov/pubmed/21244149
(3) Vendemia, J.M.C., Buzan,R.F., & Green,E.P. (2005) Practice effects, workload and reaction time in deception. American Journal of Psychology. 5, 413–429. http://www.jstor.org/discover/10.2307/30039073?uid=3738032&uid=2129&uid=2&uid=70&uid=4&sid=21101917386241
(4)Spence, S.A. (2008) Playing Devil’s Advocate: The case against MRI lie detection. Legal and Criminological Psychology 13, 11-25. http://psychsource.bps.org.uk/details/journalArticle/3154771/Playing-Devils-advocate-The-case-against-fMRI-lie-detection.html
(5) Johnson,R., Barnhardt,J., & Zhu, J.(2005) Differential effects of practice on the executive processes used for truthful and deceptive responses: an event-related brain potential study. Brain Research: Cognitive Brain Research 24, 386–404. http://www.ncbi.nlm.nih.gov/pubmed/16099352
(6) Van Bockstaele, B., Verschuere, B., Moens, T., Suchotzki, K., Debey, E. & Spruyt, A. (2012) Learning to lie: effects of practice on the cognitive cost of lying. Frontiers in Psychology, November (3) 1-8. http://www.ncbi.nlm.nih.gov/pubmed/23226137

Why being a masters student is a form of slavery

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Obviously the title of this post is a vast overstatement, and this is probably one of the biggest first world problems out there, but sometimes it really does feel that way! Okay, slaves don’t get paid for all their hard work and have no rights, but masters students pay thousands of pounds to do a year’s worth of hard work which often doesn’t get credited.

Undergraduate chemists are taught lies about how easy reactions are to carry out, and how reliably everything works if you follow the instructions properly. Experiments in undergraduate teaching labs have been tried and tested literally millions of times around the world, so you have to be a really bad practical chemist to go drastically wrong (I still managed it once or twice, though). The reality is that molecules are massively unpredictable, and when you start doing novel research, nothing tends to work!

Just today I finished a reaction with high hopes of finally getting the molecule I’ve been trying to make for about six months, only to find that no reaction had actually occurred, despite me having followed the protocol to the bone, and all I can do for now is move on and try to use another method. At least if a slave cleans the floor, the end result is that the floor is clean, not that it is just as dirty as it was at the start.

Despite this, though, when things do work in research, the overwhelming feeling of “Take that science! I beat you!!” is strong enough to give you false hope and make you keep going. That is the reason why, despite the challenges I’ve faced doing research this year, I still love chemistry and why I still want to carry on doing research as a PhD student.

Discreet Meat Deceit

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As you’re probably aware, horse meat has been found in many of the UK’s cheaper ‘beef’ products. This led to an investigation which discovered that this is happening all over Europe, including Sweden, Switzerland, Germany and France. Personally, I don’t mind, but a lot of people are creating a lot of noise about it, so it must be pretty important. I think maybe its the fact that people have been mislead. But how was the horse meat initially discovered in these products?

Horse head on cow body

Corse or How?

Some of the products tested showed a positive result for equine DNA – but if DNA is, at the end of the day, made of exactly the same building blocks in every living species on earth, how can you identify horse DNA from cow DNA from human DNA? Every individual living thing on the earth has their own unique DNA sequence (except identical twins) otherwise we’d all be clones of each other, and there are certain genes that must be present in each species in order to make them look how they do. An example would be the genes that give horses a single hoof and cows a cloven hoof on each foot, or the genes that give the horse one stomach chamber but the cow four.

The DNA sequences of many, many animals have been catalogued, and so if a sample of meat is subjected to a DNA test, you can compare the genetic material in the meat to the ‘generic’ horse genome, and if horse meat is present, you know you have it in your sample!

DNA

DNA

So, what are the implications of having horse meat in our burgers, lasagnes, etc? Horse meat is cheaper than beef in some countries, so using it can drive the price of products down. Horses are also fed a drug called bute as an anti-inflammatory, but it is actually lethal to humans at high enough concentrations, but you’d have to have a lot of it to kill you (it is still used as a last resort for extreme cases of spinal arthritis in humans – but only a last resort as the side effects are quite serious).

My opinion is that horse meat is leaner, apparently more succulent than beef, and is considered a delicacy in many countries, so maybe we should start too? Original post and personal blog at http://danthechemist.wordpress.com/2013/03/03/discreet-meat-deceit/

 

Ultra-Ever Dry

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I was recently offered a place at the Molecular Scale Engineering Centre for Doctoral Training based between Sheffield and Leeds universities, which I was more than happy to accept. Given that I will have a choice about what I’ll be doing, it got me thinking about the types of chemistry done at the centre and the applications that they have in real life. The popularity of surface modification chemistry is growing – I’m even doing some for my fourth year project – and it seems as though this area has almost limitless potential. For example, have a look at this video…

 

http://www.youtube.com/watch?v=IPM8OR6W6WE&w=560&h=315

 

How awesome is that?! The secret to this kind of technology is to change the properties of the surface to make it hydrophobic (hydro = water, phobic = fear, i.e. hydrophobic things repel water). The Ultra-Ever Dry website claims that the hydrophobic surface creates a barrier of air to stop itself from getting wet… but what does this mean?

The hydrophobicity of a surface (how hydrophobic it is) can be calculated using the contact angle it makes with a droplet of water. The contact angle is the angle between a surface and a fluid at their interface, illustrated below. Ultra-Ever Dry say that surfaces coated with their material have a contact angle of around 170 degrees, making them ultrahydrophobic. This is pretty impressive considering that a contact angle of 180 degrees would make the surface perfectly non-wetting.

Contact angles of different surfaces

Hydrophilic (water loving) surfaces have much lower contact angles than hydrophobic ones. Ultrahydrophobic surfaces have contact angles bigger than 150 degrees.

But not only do Ever Dry coated things repel water, they also repel fats and oils (making it oleophobic). If you’ve ever tried to mix water and oil, you’ll know they don’t mix, and this is because they have completely different properties – so how can this material repel both? I’ve contacted the company to see if they will reveal any more information about how it works, but it’s not likely that they will share very much.

My guess is that the molecules deposited onto the material interact so strongly with oxygen in the air that anything else that tries to reach the surface can’t get past the oxygen molecules. I’ve done my best to explain that using a crudely drawn diagram here…

The way I think Ever Dry works

My best guess on how I think Ever Dry might work based on my knowledge of chemistry now and what is said on the product’s official website

If representatives from the company ever get back to me to reveal their trade secrets, I will let you know! To find out more about me, my research and to read my other posts, you can follow this link to my personal blog: http://danthechemist.wordpress.com/

Heart attacks and hard ons

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Would you believe me if I told you that the enzyme that can prevent heart attacks is almost identical to the enzyme that gives men erections? So much so, that in 1985 during clinical trials for a drug designed to relieve high blood pressure, male patients displayed one particularly surprising side effect, and this drug went on to be one of the world’s highest grossing drugs as a cure for erectile dysfunction. That’s right – I’m talking about the little blue pill – Viagra.

Molecular structure of sildenafil
Sildenafil

Viagra (or sildenafil) was designed to inhibit (block) an enzyme called phosphodiesterase (PDE for short). There are several strains of this enzyme, each located in different areas of the body, and this drug was designed to inhibit the PDE enzyme in the walls of blood vessels resulting in their vasodilation (dilation of vessels), lowering blood pressure, and reducing strain on the heart.

Instead, the drug targeted the PDE enzyme located in the smooth muscle of the penis (PDE-5). To get to grips with how the drug works, you first need to know what an erection is (chemically speaking). Erections arise due to the build up of the molecule called cGMP in the smooth muscle of the penis. PDE-5 catalyses the conversion of cGMP to GMP to terminate the erection. Men with erectile dysfunction have over active PDE-5 enzymes and Viagra competitively inhibits PDE-5 so that the erection can be maintained.

The chemistry of an erection
The chemistry of an erection. Instead of PDE-5 converting cGMP back to GMP, sildenafil occupies the enzyme’s active site so that it can no longer do its job. Guanylate cystase is the enzyme that can catalyse the conversion of GMP to cGMP in the presence of nitric oxide.

Interestingly, there is a phosphodiesterase enzyme in the retina of the eye (PDE-6), which sildenafil can also inhibit, and This is potentially why some men observe visual side effects after taking Viagra.

There are some difficult concepts in this post that non-chemists might not understand. Please let me know and I will try and explain if you don’t get it. For the original post, follow this link: http://danthechemist.wordpress.com/2013/02/16/heart-attacks-and-hard-ons/

Why refrigerated chocolate tastes better

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The difference of opinion when it comes to whether chocolate tastes better out of the fridge or not has caused many a discussion between me and my peers, and has almost torn friendships apart (not really); but after one of my lecture courses from last semester, I can finally definitively say that chocolate DOES in fact taste better from the fridge.

First, a little background. This is all to do with a phenomenon known as polymorphism, which is the ability for a solid to exist in more than one crystal structure. Each crystal structure is called a polymorph, and each polymorph has its own set of distinct properties.

The main ingredient in chocolate, cocoa butter, has six polymorphs which can be distinguished between each other by measuring their melting points:

Polymorph I, 16-18 degrees
Polymorph II, 22-24 degrees
Polymorph III, 24-26 degrees
Polymorph IV, 26-28 degrees
Polymorph V, 32-34 degrees
Polymorph VI, 34-36 degrees

Polymorphs I – IV are not suitable for making chocolate since they are too sticky and unstable at room temperature. Polymorph VI is the most stable, but tastes bland and is too brittle. Polymorph V is the ideal form for eating (but of course, sod’s law dictates that it’s the hardest to manufacture).

This is great, I hear you saying, but why does this mean I should keep my chocolate in the fridge? Well… at room temperature, the fatty molecules in polymorph V have enough energy to slowly (days/weeks scale) convert to polymorph VI. This transformation in in the crystal structure is facilitated by the vibrational energy stored in the molecules which allow the molecules to wriggle about and realign with each other. This can be stopped by keeping your chocolate in a cool, dark place (i.e., the fridge!!) to make sure the molecules don’t have enough vibrational energy to convert to polymorph VI.

You then might ask how you can tell this has happened? The change in crystal structure is usually accompanied by something called ‘fat bloom,’ which is where the chocolate begins to look dusty, and pale spots appear on the surface as shown in the attached image. We’ve all been there (you’re incredibly lucky if you haven’t). It’s off putting, but still safe to eat. It happens because of partial melting in the solid which cases the fats within it to rise to the surface. It’s this strange occurrence that leads me to believe that keeping my chocolate in the fridge is in fact the correct way to keep it, and also why all the chocolate I bought on my exchange year in Australia just didn’t taste as good as the stuff at home in the UK due to their hotter climate!

For the original blog, follow this link:
http://danthechemist.wordpress.com/2013/02/12/why-refrigerated-chocolate-tastes-better/

A matter of inheritance

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Image courtesy of 'Digital Dreams' / FreeDigitalPhotos.net

Image courtesy of ‘Digital Dreams’ / FreeDigitalPhotos.net

The age-old ‘nature-nurture’ debate revolves around understanding to what extent various traits within a population are determined by biological or environmental factors. In this context ‘traits’ can include not only aspects of personality, but also physical differences (e.g. eye colour) and differences in the vulnerability to disease. Investigating the nature-nurture question is important because it can help us appreciate the extent to which biological and social interventions can affect things like disease vulnerabilities, and other traits that significantly affect life outcomes (e.g. intelligence). The ‘nurture’ part of this topic can be dealt with to some extent by research in disciplines such as Sociology and Psychology. In contrast genetic research is crucial to understanding the ‘nature’ part of the equation. Genetics also has relevance for the ‘nurture’ part of the debate because environmental factors such as stress and nutrition affect how genes perform their function (gene expression). Indeed genetic and environmental factors can interact in more complex ways; certain genetic traits can alter the probability of an organism experiencing certain environmental factors. For example a genetic trait towards a ‘sweet tooth’ is likely to increase the chances of the organism experiencing a high-sugar diet!

Given the importance of genetic information to understanding how organisms differ, I would argue that a basic knowledge of Genetics is essential for anyone interested in ‘life sciences’. This is true whether your interest is largely medical, psychological or social.  Unfortunately if, like me, you skipped A-Level Biology for something more exciting (or A-Level Physics in my case!) you might Genetics at bit of mystery.

Some basic genetics

Genetic information is encoded in DNA (Deoxyribonucleic acid). Sections of DNA that perform specific, separable functions are called Genes. Genes are the units of genetic information that can be inherited from generation to generation. Most Genes are arranged on long stretches of DNA called chromosomes, although a small proportion of genes are transmitted via cell mitochondria instead. Most organisms inherit 2 sets of chromosomes, one from each parent. Different genes perform different functions, mostly involving the creation of particular chemicals, often proteins, which influence how the organism develops.  All cells in the body contain the DNA for all genes, however only a subset of genes will be ‘expressed’ (i.e. perform their function) in each cell. This variation in gene expression between cells allows the fixed (albeit very large) number of genes to generate a vast number of different chemicals. This in turn allows organisms to vary widely in form while still sharing very similar genetic information (thus explaining how it can be that we share 98% of our DNA with monkeys, and 50% with bananas!).

The complete set of genetic information an individual has is called their ‘genotype’. The genotype varies between all individuals (apart from identical twins) and thus defines the biological differences between us. In contrast the ‘phenotype’ is the complete set of observable properties that can be assigned to an organism. Genetics tries to understand the relationship between the genotype and a particular individual phenotype (trait). For example how does the genetic information contained in our DNA (genotype) influence our eye colour (phenotype)? As already mentioned environmental factors play a significant role in altering the phenotype produced by a particular genotype. Explicitly the phenotype is the result of the expression of the genotype in a particular environment.

Heritability

Roughly speaking, heritability is the influence that a person’s genetic inheritance has on their phenotype. More officially it is the proportion of the total variance in a trait within a population that can be attributable to genetic effects. It tells you how much of the variation between individuals can be attributed to genetic differences. Note that this is not the same as saying that 60% of an individual’s trait is determined by genetic information. In narrow-sense heritability (the most common form used), what counts as ‘genetic effects’ is only that which is directly determined from the genetic information past on by the parents. This ignores variations caused by the interaction between different genes, and between genes and the environment. This is the most popular usage of heritability in science because it is far more predictive of breeding outcomes, and therefore tells us more about nature part of the ‘nature-nurture’ question, than the alternative (broad-sense) conceptualisation of heritability.

Uses and abuses

Genetic research can provide crucial information in the fight against certain diseases. Identifying genes that are predictive of various illnesses allow us to identify individuals who are vulnerable to a disease. This then allows preventive measures to be implemented to counter the possible appearance of the disease. Furthermore once the genes that contribute to a disease are known, knowledge as to how those genes express will help reveal the cellular mechanisms behind the disease. This improves our understanding of how the disease progresses and operates, and therefore helps with identifying treatment opportunities. In reality of course Genetics is rarely this simple. Many conditions that have a genetic basis (i.e. that show a significant level of heritability) appear to be influenced by mutations within a large number of different genes. Indeed in many cases, especially with psychiatric disorders, it may be that conditions we treat as one unitary disorder are in fact a multitude of different genetic disorders that have very similar phenotypes. Nevertheless, despite these problems genetic research is helping to uncover the biological basis of many illnesses.

One problem with Genetics, and heritability in particular, is that of interpretation. There is often a mistaken belief that a high level of heritability signifies that environmental factors have little or no effect on a trait. This misunderstanding springs from an ignorance of the fact that estimates of heritability comes from within a particular population, in a particular environment. If you change the environment (or indeed the population) then the heritability level will change. This is because gene expression is affected by environmental factors and so the influence of genetic information on a trait will always be dependent to some extent on the environment. As an example a recent study showing that intelligence was highly heritable (1) lead to some right-wing commentators using it as ‘proof’ of the intellectual inferiority of certain populations, because of their lower scores on IQ tests. Such an interpretation is then used to argue that policies relating to equal treatment of people are flawed, because some people are ‘naturally’ better. Apart from the debatable logic of the argument itself, the actual interpretation of the genetic finding is flawed because a high heritability of IQ does not suggest that environmental differences have no effect on IQ scores. To illustrate this point consider that the study in question estimated heritability in an exclusive Caucasian sample from countries with universal access to education. If you expanded the sample to include those who did not have access to education it would most likely reduce the estimate of heritability, as you would have increased the influence of environmental factors within the population being studied! Ironically therefore you could argue that only by treating everyone equally would you be able to determine those who are truly stronger on a particular trait! Independent of what your views on equality are, the most important lesson as regards genetics is that you cannot use estimates of heritability, however high, to suggest that differences in the environment have no effect on trait outcomes.

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 References

(1) Davies, G. et al (2011) Genome-wide association studies establish that human intelligence is highly heritable and polygenic. Molecular Psychiatry 16, 996-1005. http://www.nature.com/mp/journal/v16/n10/full/mp201185a.html

Although not directly cited, I found the following information useful when creating the post (and when trying to get my head around Genetics!).

Quantitative Genetics: measuring heritability. In Genetics and Human Behaviour: the ethical context. Nuffield Council on Bioethics. 2002.  http://www.nuffieldbioethics.org/sites/default/files/files/Genetics%20and%20behaviour%20Chapter%204%20-%20Quantitative%20genetics.pdf

Visscher, P.M., Hill, W.G. & Wray, N.R. (2008) Heritability in the genomics era – concepts and misconceptions. Nature Reviews Genetics, 9 255-266. http://www.ncbi.nlm.nih.gov/pubmed/18319743

Bargmann, C.I. & Gilliam, T.C. (2012) Genes & Behaviour (Kandel, E.R. et al (Eds)). In Principles of Neural Science (Fifth Edition). McGraw-Hill.

Life of a pathogen: pump some iron!

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Has somebody set up a miniature  weightlifting gym for microbes? Not yet, but just like you and I bacteria need iron to stay  alive. However, unlike us they don’t get iron as a supplement in  their cereal – they  have to find it for themselves. In bacteria  iron is needed to make proteins involved in vital processes such as  respiration and DNA synthesis. With the stakes so high they need specialised ways to get iron, and more often than not they have to  scrounge it from us, their human host.

Iron scavenging molecules (called siderophores) are one way that bacteria can get iron from a host. In the human body the levels of free iron are kept very low, so the  siderophores have to be very good at finding iron then hanging on to it (high affinity). Once they’ve done this they need to get back into the bacterial cell via special transporters in the cell membrane (see figure below).

So, send out some scavengers and get loads  of iron? Not so simple! Firstly,  the whole process takes a lot of energy for the cell. In E.coli it takes 4  different proteins just to make the siderophore, plus another 4 proteins and some  ATP (the energy currency of the cell) to get it back in again. Secondly, too much iron is toxic to the cell, so it needs to make sure that it only goes to all this trouble when it really needs to – in other words it needs some gene regulation.

This is where it gets clever.  Inside the cell there’s a protein called Fur (ferric uptake regulator) that keeps an eye on how much iron is in the cell and turns the genes for iron scavenging on and off. When there’s lots  of iron in the cell the iron binds to Fur. This allows Fur to bind to the iron  uptake genes and turn them off, so the cell doesn’t waste any resources or  overload itself with iron (see figure below). When there’s not enough iron in the cell there’s no  iron spare to bind to Fur, so Fur can’t bind to the DNA. This means that the  genes are active and the proteins for iron scavenging are made.

That’s a pretty good system, but a  lot of pathogenic bacteria take it a step further. When pathogens enter the body they need to spring into action to make virulence factors – the proteins and molecules that allow them to survive in the body and do all the  nasty things that they do. It would be a massive waste of energy if they made these all the time, so they need to be able to  activate them specifically when they enter a host. Bacteria don’t have eyes or GPS so they have to sense the environment to work out where they are. Low iron levels is one signal that they are inside a host, so it makes sense to use an iron  sensing protein to regulate other virulence factor genes (figure 3). For example, E.coli uses the Fur regulator to regulate  virulence factor genes for fimbriae (fibres which can latch onto human cells),  haemolysin (a toxin that breaks open red blood cells) and Shiga-like toxin (a toxin that helps E.coli cells to get inside human cells).

So, in the arms race of human vs. pathogen it seems that bacteria have found a few sneaky solutions this time. Not only have they gotten around the body’s iron restriction mechanisms, but they also use the low iron levels as a trigger for more deadly weapons.