Month: July 2012

Salamanders, 3D Printing and the Body Shop

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Salamanders are interesting creatures. When attacked by a predator, they will shed their tail and flee. The tail will wriggle around on its own for long enough to hopefully distract the predator and allow the salamander to escape. Fortunately, losing a tail is not a huge bother for the little guy; he’ll just grow back a new one.

Outside a select group of amphibians, the ability of vertebrate species to regenerate complex organs and body parts is extremely limited. In humans, it is almost non-existent (with the notable exception of the liver). But what cannot be done by nature, we can achieve though science! Or at the least, it may be possible in the future…

Regenerative medicine is a relatively new field that is creating new organs and new possibilities. Last month, it was reported in The Lancet that a 10 year old Swedish girl received a successful transplant of a vein grown in a lab from her own stem cells1. The girl was suffering from a liver portal vein obstruction, a potentially fatal disease. If she had been an adult, a vein would have been removed from her neck or leg and used as a replacement. However in the case of a still growing child, this procedure carries unacceptable difficulties. Instead, they grew one.

A vein from a deceased donor was stripped of all its cells and the remaining scaffold “seeded” with the girl’s own stem cells. This scaffold was then placed in a “bioreactor” which bombarded the structure with chemicals necessary for programming the stem cells to develop in a specific way. This allowed the new vein to mature before transplantation. Following a second similar procedure the girl returned to full health.

When it comes to organ regeneration experts have identified 4 levels of complexity:

    1. Simple flat structures such as skin and endothelium.
    2. Tubular structures such as blood vessels and tracheae.
    3. “Hollow” organs such as bladders.
    4. Organs with complex substructures such as kidneys or lungs.

The Lancet report is just the latest example of engineered organs being transplanted into humans. Indeed, similar results have previously been achieved with bladders, urethras and tracheae2-4. These manufactured organs have the advantage over normal transplants of being wholly compatible with the patient’s immune system, rendering the need to take dangerous immunosuppressants moot. However, whilst the scaffold technique is useful as a proof-of-concept, in practice problems can arrise. The scaffold may not be a suitable size, causing it to mismatch with surrounding tissue. The growth of cells on the scaffold may be uneven or insufficient. Furthermore, no group have yet created a level D organ using this method.

These challenges have led scientists to look for other options. 3D printing is an industrial manufacturing technique that has recently adapted and expanded into biomedical applications. A 3D printer creates objects by the process of “additive manufacturing”. The printer deposits layers of material (usually small, discrete pieces of metal or plastic) on top of one another onto a flat surface according to a programmed input. These layers are then melted together to form a complete object. This process is used to form many complex objects including machine components, jewellery and toys.

[youtube http://www.youtube.com/watch?v=hk8u5CefYsc]

 

Very recently, 3D printers have become capable of laying down material at the micrometre resolution (one-thousandth of a millimetre), a scale which allows accuracy at the level of a single cell. Biologists have since been experimenting with using 3D printers to print human organs. Small clumps of cells are bound together with a rapidly-degrading film that allows these clumps to be printed three-dimensionally in a fairly structured manner. The cells are then deposited in a shape and structure similar to a specific organ. Whilst the arrangement of the printed cells is not quite the same as a naturally occurring organ, the cells are able to detect their environment and re-organise themselves into a more conventional structure. One example is shown below.

Large blood vessels are generally composed of the following: from the centre outwards, the internal empty space (the lumen), the internal barrier (endothelium), then smooth muscle cells and finally the fibrous tissue. a) The template (top) shows printed cylinders of smooth muscle cell stacked on top of each others. The result (bottom) shows that over time the cells assembled automatically in a manner that produces a lumen. b) The template (top) shows printed cylinders of mixed smooth muscle cells (red) and endothelial cells (green). A cross-section of a mature blood vessel shows that over time the endothelial cells migrate towards the centre. c) Top showing a template consisting of fibroblast cells (red) and smooth muscle cells (green). A cross section of the resulting blood vessel showing clear fusion and segregation of the two cell types. From Jakal et al.5

The printed cells used for this technique can either be specific cell types as shown above or more generic stem cells. Once 3D constructs have been formed, the tissue is maturated in a bioreactor to form a stable organ, similar to previous techniques. The now consolidated organ is essentially functional and in theory could be used for transplantation. However, such is the novelty of this technique that it hasn’t yet been put into practice.

Bioprinting has huge strengths over similar techniques including customisation, flexibility and reproducibility whilst not relying on donor material. In theory any cell type, body structure or tissue may be used in this technique providing the correct design and the correct type of “ink” is used. Even bone may be printable using a combination of osteogenic cells and temporary connective tissue replacements.

The potential for this technology is vast. Imagine if we were to bear the maximum fruits of regenerative research. Organ donor waiting lists would become a thing of the past. No more children on dialysis. No more diabetics on insulin. No more hormone disorders (we could replace faulty hormone-releasing organs). Men and women injured in wars or in car crashes would have limbs replaced or healed.

And what about non-therapeutic uses? Want a breast implant? No need to implant a silicon or saline bag – just add more breast. The number of animals killed for research purposes would greatly decrease. When you can test drugs and conduct experiments on organs grown in a lab, the need to extract these organs from animals would no longer exist.

Whatever the possibilities may be, research is still at an early stage. Printers of adequate sophistication cost in the range of tens of thousands of pounds, choking research in this area. We can only hope that as prices collapse, so will the barriers to progress.

Post by Chris Logie

References

1.     Olausson M. et al. (2012). “Transplantation of an allogeneic vein bioengineered with autologous stem cells: a proof of concept study.” Lancet 380 9838:230-7.

2.     Atala, A. et al (2006). “Tissue-engineered autologous bladders for patients needing cystoplasty”. Lancet 367 9518:1241-6.

3.     Raya-Rivera, A. et al. (2011). “Tissue-engineered autologous urethras for patients who need reconstruction: an observational study.” Lancet 377 9772:1175-82.

4.     Macchiarini, P. (2009). “Clinical transportation of a tissue-engineered airway.” Lancet 372 9655:2023-30.

5.     Jakab, K. (2010). “Tissue engineering by self-assembly and bio-printing of living cells.” Biofabrication 2 2:022001

6.     Fedorovich, N. E. (2009). “Organ printing: the future of bone regeneration.” Trends Biotechnol 29 12:601-6

Politics vs. Science – from Galileo to Professor David Nutt

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In 2009 Professor David Nutt caused controversy for the UK government’s Advisory Council on the Misuse of Drugs after stating the cannabis should be declassified to a Class C (rather than Class B) illegal drug.  During his time on the Council, Prof. Nutt had also claimed that recreational use of ecstasy is less dangerous than horse-riding. He was sacked from his government-advice post by Alan Johnson, the then Labour UK Home Secretary, who wrote to Nutt, “I cannot have public confusion between scientific advice and policy and have therefore lost confidence in your ability to advise me as chair of the ACMD.” By that logic, Johnson must have breathed a huge sigh of relief when three more scientist experts on the Council soon resigned.

Science and politics share a very complicated relationship, and have done since time began. Galilieo was condemned for stating that the Earth revolved around the sun. He was kept under life-long house arrest for his theory. Darwin’s theory of evolution has been exploited as an argument for any number of political agendas, all the way from communists to Nazis. Global warming was (and still is) a political minefield for climate scientists. The disciplines of science and politics are so intertwined such that good science is intrinsically political and policies should always be informed by science. Unfortunately, in today’s society there is a massive disconnection between scientists and politicians.

This rift is exemplified by the shocking fact that there is only one British Member of Parliament out of 650 that has a scientific, research-based PhD (Lib Dem MP for Cambridge Julian Huppert, Biological Chemistry, in case you’re wondering). Similarly in the United States, 3 in 435 people in the House of Representatives have a non-medical, scientific background. And considering Prof. Nutt’s dismissal, it seems that scientists are seen by politicians as commodity experts whose advice can be cherry-picked for a bit of ‘policy-based evidence-making’. Winston Churchill once said that science should be ‘on tap but not on top’. But what’s stopping us scientists from getting properly involved in politics?

I’m tempted to argue that, to a certain degree, it’s our own fault. As scientists, we are notoriously rubbish at PR. I imagine many of us wouldn’t want to be seen dead testiculating* with the rest of the mob in Parliament. Sadly, a lot of scientists’ work is viewed as slow, expensive, secretive and not immediately socially beneficial. The current stereotype of a scientist is sadly pretty much the same. Politicians, on the other hand, work to very tough deadlines in order to combine ethical, social, moral and economic factors into their party’s policies. These policies actually make a huge difference to people’s daily lives. As if that wasn’t enough, politicians have to try and kiss babies, refrain from calling women bigots and avoid cameras when beating up youths during the Election. Makes the lab seem pretty cushy.

The main thing scientists have got going for them if they fancy residing in Downing Street is the doctrine of science itself. As Carl Sagan (the American Brian Cox of his time) said, “science is a way of thinking much more than it is a body of knowledge”. The knowledge bit isn’t bad either and it lasts far beyond the sell-by date of parties’ policies.  The logic that underlies the analysis of data gathered from random, blinded, controlled trials is the perfect way of objectively testing different policies. And we’ve got buckets of that logic to share with our MPs.

U.S. President Barack Obama praises his ‘dream team’ of scientific advisors for their advice, “even when it’s inconvenient, indeed, especially when it is inconvenient”. As scientists we may not have rhetoric on our side to sugar-coat the facts; but shouldn’t that
be an advantage? We should not just be ready to inform and educate policy-makers; we should be ready to objectively challenge their decisions. In return, politicians shouldn’t dispose of us when they don’t like what we have to say. Professor Nutt hasn’t given up; he has now formed the Independent Scientific Committee on Drugs (win). Personally I think he sets an outstanding example to both scientists and politicians alike.

*to testiculate (verb): to gesture animatedly whilst spouting absolute b*llocks.

Post by Natasha Bray

How Do Diet Pills Work?

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At the moment my life seems to have turned into a horribly gender clichéd romcom, in which I need to lose weight to get into an oh-so-special dress for a wedding. Imagine if you will, the voice-over guy introducing the trailer to my life, ‘Liz Granger is too tight-fisted to buy a new dress, but Liz Granger is about to find out sometimes losing weight to fit into an old dress isn’t as easy as it seems. Can Liz do it? Maybe with a possible love interest, some good friends, a little motivation and an exercise montage…she just might.’ I’m lining up Jen for the role.

Turns out the obstacle in this film would be the fact I like crisps, drink too much wine and avoid exercise.  So what’s a girl (or boy) to do?  There must be a quick fix answer, surely. Well, my fascination with everything that allows you to procrastinate on the internet has led me to some rather shady websites that peddle weight loss pills that promise you can lose a stone in two weeks. With this in mind I decided to look into the ‘science’ of how diet pills work – after all if they look like a real medicine they must work like a real medicine. Maybe I’m just thinking of the placebo effect there. Anyway these are some types of pills I found that you can pop à la the internet:

Laxatives

Yes, apparently if you want to lose weight you need to poop and you need to poop a lot. I can’t quite fathom this one, but I guess the logic is that if the food passes through you quickly enough it doesn’t get absorbed in your intestines. I can’t help but think it would be more pleasant to just eat healthily and not have diarrhoea, but I’m old-fashioned like that. A lot of the herbal diet pills you can buy are actually just weak laxatives and diuretics (diuretics make you pee more). Maybe if it’s natural it’s not as gross.

Caffeine

Most diet pills have caffeine in; there is evidence to suggest caffeine suppresses appetite and it certainly peps you up. I’m not convinced though, I drink a lot of coffee and I don’t think it’s making me any thinner. But then again, maybe if I didn’t drink coffee I’d be the size of a blimp. I’m guessing the caffeine just makes you feel like the pills having some kind of instant positive effect on your energy levels.

Fat Burners and Appetite Suppressants

This is a weird one. Lots of the active ingredients found in diet pills have some evidence to suggest they suppress appetite but they are also often marketed as ‘fat burners’ that speed up the metabolism.  Other fat burners have vague ingredients like ‘açaí berry extract’. Maybe they do burn fat, it’s difficult to say, but with most evidence (when there is evidence) being anecdotal rather than from a controlled trial, I’d be sceptical.

Incidentally, açaí berries are the fruit world’s answer to beefcake the powdered form is a third fat, and 100g of the powdered berries gives you 530 calories – twice as many calories as the same amount of French fries from McDonald’s. The main selling point of açaí berry extract is that it’s supposed to speed up metabolism because it is full of antioxidants. One of the most potent antioxidants that exist is vitamin C, so if consuming antioxidants makes you lose weight, you’d be better off buying a 90p packet of vitamin C tablets. But truth be told, you’d pee most of the vitamin C out and this is almost certainly what would happen with the vitamins in powdered açaí berry. So if I took them I’d pee out most of the goodness but I would still absorb the calories – brilliant.

 A compound called Phentermine is found in a lot of diet pills. It affects the fight or flight chemical messenger in the brain called noradrenaline (norepinephrine for Americans) and this is thought to suppress hunger. Its actions in the brain are actually pretty similar to those of a family of drugs that include amphetamine. You remember amphetamine, that illegal drug of abuse that is heavily addictive? Although Phentermine is considered a little safer than amphetamine it is still associated with high blood pressure and can affect the heart rate. During most of the 1990s a lot of diet pills contained Phentermine paired up with another compound called Fenfluramine – together they combined forces to make Fen Phen.  After around 10 years on the market Fen was linked to heart disease and was banned. I don’t know about you but that makes me a bit more cautious of diet pills in general.

A popular pill ingredient is p57 derived from a plant called Hoodia. Although there is evidence to suggest it can affect signalling in the brain and suppress the appetite of rats, the rats in question were injected with the molecule directly into their brain. So unless you’re going to inject your brain with p57, (to be clear no one should EVER do that), I’d take that with a pinch of salt.

Another potential appetite suppressant is an ingredient called 5HTP. Your body can convert 5HTP into serotonin, an important chemical messenger in the brain that controls mood and appetite. The problem is that taking in a lot of 5HTP doesn’t necessarily mean it will be made into serotonin. The body has some awesomely complex and amazing mechanisms for keeping all the hormones inside you balanced at the right level. Even if the building blocks for serotonin are available, it doesn’t mean it will be made into it so there’s a good chance you’ll just excrete it (hopefully without the aid of a laxative).

Fat binders

Regular laxative-induced diarrhoea not sexy enough for you? Why not try uncontrollable oil seepage. That’s right, seepage. Fat binders, unsurprisingly, bind to fat and stop it being absorbed. And when it’s not absorbed guess where it goes? These pills tend to make people avoid fatty food for obvious reasons, which also helps with weight loss. It’s pretty crazy we live in a society where people have to be scared of oil seepage to stop eating fatty food. Now where did I put those crisps….

My Options

So, here are my options: something that makes me go to the loo a lot, something that makes me poop fat, a questionable concoction herbal and non-herbal compounds that may or may not work but cost quite a lot of money and finally, lots of caffeine. It’s almost like eating sensibly and exercising might be an easier option.

It’s OK though, the conclusion to my movie is that I gave up and bought a dress that fits me. Don’t get me wrong I’m pretty happy with my size – there’s way too much pressure for women (and men) to be slim for superficial reasons. But thinking about all this did make me want to get healthier because basically I don’t want to get cancer, diabetes, heart disease or any of the other many weight- related diseases.  With this in mind I am going to start exercising more, try to kick the crisps habit and cut down on the wine. I definitely won’t be taking any diet pills, because even if they do work there is no way it is healthy to lose a stone in two weeks, no matter how much you don’t want to shell out for a new dress.

Post by Liz Granger

Twitter: @Bio_Fluff

Science: Is it a girl thing?

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Last week I was forwarded a link to a, now withdrawn, advert from the European Commission. The link came from a friend with a wry sense of humour and when I first watched the clip I automatically assumed it was a tongue-in-cheek social commentary aimed at rubbing ‘feminist types’ up the wrong way. To me it seemed to play on a negative female stereotype (the fashion-conscious airhead), accentuating how this attitude does not fit with the otherwise serious, male oriented, world of science. The women in the advert were all immaculately preened and shown dancing around in short skirts and high heels, whilst the only legitimate looking scientist was a male sporting a lab coat and staring studiously down a microscope (see the clip below). It was later I realised that, far from being a cheeky misogynist jibe, this was an actual advert produced by the European Commission aimed towards encouraging young women to study science.

[youtube http://www.youtube.com/watch?v=g032MPrSjFA]

 

It seems, after extensive market research, the European Commission decided this was the best way to foster an interest in science amongst young girls. I assume their research showed that a large proportion of young women are more interested in fashion, beauty and music than differential equations and scientific method. Therefore, they ‘logically’ deduced that: to encourage more women into scientific careers, they had to show how glamourous and sexy this career choice can be. On the surface this makes sense: if you want to market a product (a scientific career) you have to make that product appeal to your target demographic (young women). However, it is not too hard for me, a female scientist, to see how this approach is short-sighted.

The life scientific is one of massive contradiction. Most people only know the romanticised/glamorised view of science as seen on TV: white coats, test tubes and Brian Cox staring knowingly into the middle distance. This view of science is easy to fall in love with. However, look beyond the inspirational sound-bites and you will find the true heart of science; the scientists. Very few of us are your stereotype ‘super genius’ and, as with any worker, we struggle on a day to day basis with insecurity, doubt and frustration but the one thing I believe we all share is an unwavering curiosity and determination, since without this we would undoubtedly fall to the pressures of our field. This curiosity and determination is the key to becoming a successful scientist and something the European Commission’s marketing ignores. Therefore, although the campaign may encourage more young women to study science, if these women enter the field believing a scientific career to be no more than a glamourous asset they can flaunt with their girlfriends over a late lunch, the outcome will undoubtedly be some rather disillusioned women and a number of ineffectual scientists.

That said, although I disagree with the their approach, I cannot deny that there is a lack of women in the higher levels of academia, indeed this is true for the higher echelons of many careers. This is undoubtedly a problem which must be addressed. However, I believe that before we stand a chance of readdressing the balance we must first uncover where the problem actually lies.

As a postgraduate student in the biological sciences, I don’t see a large divide between the number of male and female students in my field and level of study. However, there are undoubtedly fewer women holding higher academic positions (e.g. professor-ships) in this field. Conversely an area where you can see a vast male/female divide, starting as early as A-level, is in the physical sciences. A (male) friend of mine studied physics at university and often recants how there were so few women in his department that they had to organise socials together with the psychology department to ensure a good male/female balance.

statistics from the UKRC and the Athena SWAN charter, in the period spanning 2007-2009
statistics from the UKRC and the Athena SWAN charter, in the period spanning 2007-2009

 

This raises two questions: firstly, what is standing in the way of women achieving higher academic positions and secondly why do fewer women choose to study the physical sciences and maths?

The first question may simply reflect the fact that, historically fewer women chose the scientific path. Therefore at the higher levels of these fields, where the practising academics tend to be older (40 or above), the more recent influx of women is yet to filter its way up. However another explanation, indeed one that I grapple with on a regular basis, is that there is something about the academic lifestyle which does not appeal to the female mentality.

As I mentioned earlier, the life of a scientist is a constant battle. We spend most our time forming and testing theories, many of which only lead to more questions. Then, once things begin to slot into place, we are expected to defend our methods and findings against the rest of the community, which can often lead the poor researcher back to the drawing board. Although this process is certainly not pleasant it is necessary to ensure our theories are scientifically accurate, especially since mistakes can have devastating consequences. This means that good researchers are not only thick-skinned but also highly motivated, determined and willing to dedicate the majority of their time to their work.

Along with these pressures, the financial rewards of a scientific career are often small. To gain a typical Ph.D. from a UK university the student must first have spent at least three years as an undergraduate, more often four including a Master’s degree (we all know this is an expensive endeavour, more so recently). A typical Ph.D. course lasts an additional 3 years, during which it is rare to earn more than ~£16,000 p.a. Most courses offer an optional unpaid 4th year, which many students (even the most organised and diligent) often use to finish their thesis. Assuming you can defend your work and gain a Ph.D. this qualification usually leads to one of two academic career paths: either a side-step into industry (an area I’m not so qualified to speak about) or a move into a ‘postdoc’ position, usually with the ultimate goal of gaining permanent academic employment. Unfortunately, despite the sheer amount of effort required to reach this stage, postdoc jobs are usually temporary (often lasting only 3-4 years) and do not tend to be highly paid. It is also not rare for a researcher to move through three or more postdocs before finding a permanent position. This means that many researchers are expected to spend the whole of their twenties and often a good proportion of their thirties in relatively low paid, high stress, temporary positions.

[youtube http://www.youtube.com/watch?v=XViCOAu6UC0]

Don’t get me wrong; although this may sound bleak, for the right person, science is an ideal career. For the most part you get to be your own boss, you are constantly challenged by new problems, you get to travel around the world presenting your data at conferences and you know that your work is of huge significance to the community, even if it’s just a small part of a larger picture. However, for many people the lack of stability and a sustainable work/life balance will undoubtedly become a stumbling point.

In my experience women are more likely to struggle in positions which do not offer a sustainable work/life balance, especially if they intend to start a family. This may be why you find a large number of female academics moving sideways into more flexible careers such as teaching or medical writing (a predominantly female profession). In my opinion, the high attrition rate of women in the biological sciences does not reflect a difference in intellectual capacity or capability but simply a difference in priorities; men are perhaps more willing to sacrifice relationships and financial stability for their work. If this is the case, I believe there is a problem with a system which allows a number of intelligent motivated scientists who want a more balanced lifestyle to simply fall by the wayside.

The second question (why at most ages there are fewer women studying the physical sciences and maths) stabs at the heart of the age old nature/nurture debate. As far as I know, we cannot say whether the female mind is less inclined to this type of thought or whether the environment in which young girls grow up discourages them from studying these subjects. Either way, I believe the key to tackling the imbalance lies in fostering an interest in these subjects early in life rather than trying to convince teenagers that science is ‘cool’. Indeed, I think a good start would be to provide young girls with some more realistic academic female role models!

– but hey, don’t ask me I’m just a girl…

Post by: Sarah Fox and Louise Walker