Basic Research – What’s the Point?

Posted on May 19, 2013 by biofluff

I am what is known in the research trade as a ‘basic’ researcher. It’s not that my work is simple. What basic research means is that the work doesn’t have any immediate real world application.

In some people’s eyes that means it’s not useful, or ‘research for the sake of research’. In my opinion it’s pretty exciting – I look at how and more importantly why things move around inside cells. Intrigued? Read about it here.

These scientists might be doing basic research, just don't ask what's in the tube.

These scientists might be doing basic research, just don’t ask what’s in the tube.

Some research has direct applications – researching new drugs, new technology, the effect of various factors on health and the environment, you know – ‘useful stuff’. The thing about all of that research is that it has its foundations deeply rooted in knowledge gained from basic research.

Now don’t get me wrong I like the stuff that comes out of ‘useful’ research. I’m keen to find out how many rashers of bacon I can chow down on before I’ll get cancer. If I get ill I’d definitely want a new drug that could treat me. I’m eager to find out how much we’re screwing up the planet. Research that translates to the real world is awesome. I just think basic research should get more credit, or at least less flack, for contributing to science and our understanding of how things work.

Most importantly, basic research deserves to get funding. Not just because it’s interesting, but because we don’t know what useful things may come out of it one day in the future. If BuzzFeed has taught me anything, it’s that a point is always made best in the form of a list. So here are my ‘Top 3 Basic Research to Real World Breakthroughs ’. Catchy name, no?

1.       The Structure of DNA

DNA_double_helix_45Raging misogyny and racism aside, if Watson and Crick hadn’t taken Roselyn Franklin’s data without her permission* and worked out the structure of DNA…well someone would have probably worked it out eventually. But that doesn’t take away from their combined genius in solving the structure. They also did ground breaking work to discover how genes in DNA are made into protein. Intellectually speaking they were/are pure brilliance.

Now, this may all seem applicable to the real world in the first instance but when you think about it, Watson and Crick wanted to know the structure of DNA and how it worked purely for the knowledge. When they made this humanity-changing intellectual breakthrough, they had no idea that one day our knowledge of DNA would lead to huge leaps forward in medical diagnosis and treatment, or for that matter the ‘Who’s the daddy?’ paternity tests of Jeremy Kyle. The latter is more important. Obviously.

2.       The discovery of cellulose.

800px-Plastic_objectsCellulose; everyone’s favourite plant based, un-digestible polysaccharide. I’d guess when Anselme Payen discovered this polymer in 1838 he was just really psyched to find out more about the molecules in plants. I’d certainly be surprised if he envisioned that one day cellulose would pave the way for polymer science and one of our greatest inventions – plastic. Don’t think plastic is terrific? Look around you– how much stuff is made out of plastic? Plastic has made manufacturing easy. The discovery of cellulose as a natural polymer aided polymer research in years to come, most notably the Nobel Prize winning work of Hermann Staudinger. In turn, understanding polymers provided a means to produce many different and useful types of plastic that we can use to make stuff cheaply and easily.

3.       Radioactivity

Radioactivity_symbolMarie Curie. She was one seriously cool lady. Alongside her also very cool husband, Pierre, she discovered radioactivity.  After years of toil they purified and discovered polonium and radium. The research was unquestionably driven by the desire to simply understand what radioactivity was. The work has been instrumental in helping us understand basic physics at an atomic and sub-atomic level. Despite this, the research Marie and Pierre did has given rise to many real world changes including nuclear energy, medical treatments such as radiotherapy to treat cancer, alongside uses in sterilisation of food and other fields of research.

So there you have it, my ‘Top 3 Basic Research to Real World Breakthroughs ’. But there have been way more. What have I missed out? What would go on your list? Let us know in the comments below.

Post by: Liz Granger

*This is only one side of the story. Read more about the dynamic between Rosalind Franklin, her colleagues and Watson and Crick, here and here.

Posted in Liz Granger | 2 Comments

Acne bacteria to blame for back pain?

Posted on May 12, 2013 by thebrainbank

What do acne and chronic back pain have in common? Well, as it turns out, more than people once thought.  A group at the University of Southern Denmark have found that the same bacteria that gives people spots might be to blame for up to 40% of patients with lower back pain. What’s more, these infections can be treated with antibiotics.

Slipped disc popping out from in between the evenly grey vertebrae

Your backbone is a column of alternating vertebrae (bones) and intervertebral discs (cushions). The bones provide the strength and support, while the cushion discs allow movement and flexibility. Occasionally, thanks to a mix of age and awkward movement, the disc can bulge out from between the bones. In some cases the jelly-like goo in the disc’s centre, called the nucleus, can even ooze out – a bit like thick jam leaking out of a doughnut. If the nuclear material or the disc itself puts pressure on nerves coming in and out of the spine, it can be even more painful.

Slipping a disc is, by all accounts, excruciating, but it usually starts to heal by 6-8 weeks. However, someone can be diagnosed with chronic back pain (CBP) when the pain doesn’t subside after three months. Trouble is, this happens all too often, with an estimated 4 million people in the UK suffering from CBP at some point in their lives. The cost of CBP to the NHS is about £1 billion per annum. This doesn’t even cover lost working hours or the loss of livelihood suffered. Treatment usually focuses on relieving pain, preventing inflammation and more recently, cognitive behavioural therapy to treat the patient’s psychology, especially if the organic, physical cause of the pain is no longer obvious.

Recently, scientists in Denmark found a really important link between the bacteria responsible for acne, known as Propionibacterium acnes (P. acnes) and bad backs. The researchers found that in about half of their patients with slipped discs, the disc itself was infected, usually with P. acnes. A year later, 80% of the infected patients – compared to 43% of the uninfected patients – had dodgier bones either side of the slipped disc than 12 months before. The affected bones had developed tiny fractures and the bone marrow was replaced with serum, the liquid found in blisters.

Acne is not to blame for bad teenage hairstyle choices.

So how did the discs get infected? Bacteria like P. acnes get into our bloodstream all the time, particularly when we brush our teeth or squeeze spots. P. acnes and other similar bacteria don’t like oxygen-rich environments and so don’t normally grow inside us. The spinal disc doesn’t have a lot of oxygen around, providing a perfect home for the bacteria. If the disc is damaged – say, after popping out from the spinal column – tiny blood vessels sprout into it, letting the bacteria move in and settle down.

There, the bacteria grow and, rather than spread anywhere else, they spit out inflammatory chemicals and acid. The acid corrodes the bone next to the disc and causes more swelling and pain around the area. This discovery is ground-breaking, since before this research it was thought that discs couldn’t get infected except in a few exceptional cases.

The Danish researchers then conducted a second study, testing whether simple antibiotics could get rid of these bacteria and therefore treat chronic lower back pain. Patients that already had the characteristic signs of bone inflammation (tiny fractures and swelling) were given a 100-day course of antibiotics. The patients were reassessed a year after the trial began. Patients treated with antibiotics reported less pain, less ‘bothersomeness’ (yes!), took fewer days off work, made fewer visits to the doctor and, crucially, their bones looked in much better nick than the patients given a placebo.

Considering the huge numbers of people who are affected by chronic back pain, and the cost of treatments like surgery versus a course of antibiotics, this discovery has been glorified as the stuff of Nobel prizes. The revelation that bacteria are to blame for this mysteriously untreatable condition rings familiar. It has been likened to the discovery of the culprit bacteria behind stomach-ulcers, Helicobacter pylori. Like back pain today, stomach ulcers were dismissed for years to be a disease of the mind, endemic among stressed-out melodramatics or people who ate too much spicy food. (And yes, Barry Marshall did get a Nobel Prize for swallowing a Petri-dishful of H. pylori.) It would be fantastic if, instead of resorting to surgery, half a million CBP patients could be effectively cured within 100 days or less!

The bacteria in the plate on the right have become resistant to many of the antibiotic white spots and so are more widespread.
Photo by Dr. Graham Beards

Unfortunately, there is a downside. Antibiotics have long been the magical cure-all, but just like fossil fuels, housing and talent on TV, we’re running out. Bacteria are becoming resistant to antibiotics faster than we can create new, effective ones. It’s an arms race and we’re losing, very quickly. What’s worse is that because of the recent negativity surrounding over-prescription, there are now restrictions on giving patients broad spectrum antibiotics. Since antibiotics can’t be used as much as they were 30 years ago, pharmaceutical companies can’t make any profit from developing new ones. And so, to further compound the problem of antibiotic resistance, there are fewer and fewer antibiotics being created every year.

In 2000 alone, UK doctors made 2.6 million prescriptions of antibiotics for acne. One study by a group in Leeds looked at the number of acne patients who were infected with P.acnes and were resistant to at least one type of anti-acne antibiotic. Between 1991 and 2000, the fraction of acne patients with antibiotic-resistant bacteria rose from about a third to more than a half.

The discovery that acne bacteria might be to blame for so many cases of debilitating back pain is hugely important. However, it also highlights how dependent we are on our dangerously dwindling supply of effective antibiotics, and how we might be wasting antibiotic effectiveness on comparatively trivial conditions such as spots.

Post by: Natasha Bray

Posted in Natasha Bray, Uncategorized | 6 Comments

Comments: The future of secondary school science

Posted on May 6, 2013 by thebrainbank

Exam time is fast approaching and once again this year pupils will not only be fretting MH900410098about their potential grades, but also over the following inevitable barrage of claims concerning falling exam standards. Yes, however hard you may have worked for that A* to C grade, according to the tabloids, your efforts were futile. Particularly since modern GCSEs are now little more than the academic equivalent of an award for ‘taking part’ – spell your name correctly and walk home with a qualification. But we all know that this is not really the case, that the real situation is significantly more complex.

The truth is, contrary to what we hear from politicians, comparison of exam standards is not an exact science. A seminar held in 2010 by the examinations group Cambridge Assessment concluded that “it is not possible to compare standards, definitively, over long periods of time and perhaps attempting to do so is simply confounding the problem.” Professor Gordon Stobart, from the Institute of Education compared the debate over exam standards with climbing Mount Everest noting that: “In 1953 two people got to the top of Everest, an extraordinary achievement at the time. Yet on a single day in 1996, 39 people stood on the summit.” Does this mean that the mountain is getting easier to climb? Not necessarily, it may simply reflect the fact that more people are attempting the climb and that those who do so are now better equipped.

MH900401121I took my GCSEs around 12 years ago and still remember feeling my success was tempered by claims that exams were ‘getting easier’. I can certainly vouch for the fact that they didn’t feel easy! But, then again, I had nothing to compare them to since, at that time, they were the hardest exams I’d ever taken. Interestingly, the small amount of research which exists in this area shows modern GCSEs are not equivalent to their predecessors the O-levels. A study by the Royal Society of Chemistry (the Five Decade Challenge) found that current students had a harder time answering exam questions taken from the old O-level syllabus than questions written after the GCSE switch-over. The scores for all GCSE-style questions, irrespective of date, remained relatively stable. The study found that students performed well on tests of recall but found problem-solving and tests of quantitative skill challenging.

There are many explanations for these and similar results. It is possible that exams are getting easier. However, it’s equally possible that changes to the syllabus and style of question mean that modern students show different strengths than those required to answer O-level style questions.

MH900402266Anecdotal accounts argue that a culture of ‘teaching to the test’ means that modern students are encouraged to play the system, favouring lessons on exam technique over studying all available material. A particularly worrying example of this can be seen here. To be honest, I do remember a lot of emphasis being placed on past paper learning, knowing how to answer questions and rote learning of facts and figures – something I’m actually pretty terrible at. Add to this a survey by the Confederation of British Industry showing that “more than four out of 10 employers are unhappy with youngsters’ use of English, while 35% bemoan their numeracy skills” and the notion that lecturers often complain about students’ lack of initiative, a worrying picture starts to emerge.

Wherever the problems lie, I believe that it is unfair to blame the students for these failings. Constantly reminding them that the exams they agonised over for the last few years were ‘easy’ won’t solve anything and at worst could be damaging. I also doubt teachers are at fault; they are instead victims of a culture that craves an end result without caring how it is achieved. Instead, we need to take a long hard look at the current system itself and decide whether or not it is still fit for purpose. Luckily this is exactly what education secretary Michael Gove is doing right now. In a recent letter to Ofqual he argues that that “there is an urgent need for reform, to ensure that young people have access to qualifications that set expectations that match and exceed those in the highest performing jurisdictions.”

He is embarking on a mammoth task, which I certainly don’t envy. Not least when it MH900426563comes to science education. With public debate ranging from GM crops to vaccinations, scientific understanding is a must in today’s society. Especially since it has been argued that individuals without a working appreciation of science are more likely to be swayed by pseudo-science and unfounded propaganda. Therefore, providing our children with a strong working understanding of basic science is a must.

Unfortunately I worry that Mr Gove’s reforms run the risk of ‘missing the mark’ when it comes to science. They appear to concentrate heavily on standardising the format of secondary school teaching, removing emphasis on coursework and ensuring qualifications are “linear, with all assessments taken at the end of the course.” This may indeed provide “qualifications that set expectations that match and exceed those in the highest performing jurisdictions.” However, I worry it will fail to tackle the true failings in our current science curriculum.

The Science and Technology Committee Report of Science Education – 2002 states that: “the current curriculum aims to engage all students with science as a preparation for life. At the same time it aims to inspire and prepare some pupils to continue with science post-16. In practice it does neither of these well.” Even more damning is the report’s observations on course structure. It states that “practical work, including fieldwork, is a vital part of science education. It helps students to develop their understanding of science, appreciate that science is based on evidence and acquire hands-on skills that are essential if students are to progress in science.” However, it recognises that due to pressures and time constraints placed on teachers, coursework now has “little MH900448347educational value and has turned practical work into a tedious and dull activity for both students and teachers.” From this they conclude that “many students lose any feelings of enthusiasm that they once had for science… neither enjoy or engage with the subject… they develop a negative image of science which may last for life.” And I can’t see this situation improving if reform means more emphasis on achievement in a final exam and less emphasis on continuous coursework assessments.

The proposed system may place more pressure on teachers to maintain standards through exam achievement alone, running the risk of exacerbating our ‘teach to the test’ culture and marginalising the significance of practical skills development. I hope that if these changes are thoughtfully implemented such problems may be avoided. However, the outcome of this still remains to be seen.

I wonder if there is scope for the scientific community to become further involved in secondary school science education. Successful projects such as I’m a Scientist Get me Out of Here are already gaining in popularity. But, there is still much more we can do. For example: developing online e-learning resources covering the basic curriculum whilst also enabling active scientists, working in related fields, to communicate with students through blogs and forums – placing the curriculum on the context of real-world research. I know scientists are concerned about how their subjects are taught, so perhaps it’s a good time to start building better links with schools and really getting involved?

Post by: Sarah Fox

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The dream-reading machine

Posted on April 27, 2013 by thebrainbank

The film Inception starts with Leonardo DiCaprio and Joseph Gordon-Levitt attempting to infiltrate someone’s subconscious. They are trying to steal the target’s dreams. This wonderfully futuristic concept may be a thing of science-fiction movies, but researchers in Japan might just be on the road to seeing what you dream.

Research carried out by Yukiyasu Kamitani’s group at the Advanced Telecommunications Research Institute in Kyoto, published in the journal Science, used an fMRI (functional magnetic resonance imaging) brain scan to monitor volunteers’ brain activity whilst they drifted off to sleep. By creating a computer algorithm to predict what this brain activity meant, they were able to predict what a subject was dreaming about.

To begin, 3 volunteers were placed into an fMRI scanner and shown Google images of many different objects. The activity in the visual areas of the brain was monitored by the scanner and uploaded to a computer. Words associated with each of theses images were processed and arranged into groups of like-meaning words, called synsets. For example, words such as Structure, Building, House and Hotel would be grouped together in their own synset. Words within a synset were ranked depending on their importance, and the most important was used to describe that synset. For the example above, the word Building would be the highest ranked word in that synset. This allowed them to narrow down a number of possible words/objects to one word of ‘best-fit’.  Images of houses, hotels, offices, would all be narrowed down to Building.

The computer was given information of the synsets that related to each image, along with the brain activity at the time that image was shown. This allowed the researchers to match brain activity to certain images and words. The computer now knew that when the subject saw a picture of a house, their brain responded in a certain way. This brain activity was grouped together with activity when the subject sees an office, and a hotel etc.

Now came the real test. By categorising brain activity based on what a person sees, could they read what a person was dreaming about? The 3 subjects were placed in the scanner and told to fall asleep if they felt tired. The electrical activity of their brain was recorded by EEG (electroencephalogram) in order to see when they fell into the early stages of sleep. During these early stages, one does not normally have vivid ‘dreams’ but typically light hallucinations.

As these hallucinations started, the brain activity in visual areas was recorded and run through the algorithm. The algorithm came up with the synsets that were most likely to be represented by that brain activity, and used the Google images from before to present a video of what it thought the person was ‘dreaming’ about. This can be seen in the video below. To test how accurate the computer was at predicting the ‘dreams’, the volunteer was awoken and asked what they had just seen.

When the researchers compared what the participants reported they were seeing with the computers prediction, they found that the computer was correct in 60% of cases. This is significantly higher than getting it right by chance. The computer was able to use brain activity during the early stages of sleep to read and predict what the volunteer was seeing.

This study is not without its limitations. Firstly, what most of us see as ‘dreaming’ is not thought to occur in these early stages. We believe ‘dreaming’ occurs mainly during rapid-eye movement sleep, a stage of sleep that occurs around an hour later than these early stages of sleep (see below). What are measured here are hallucinations that occur when we are falling to sleep. Furthermore, an fMRI machine is incredibly loud due to its large, spinning magnets. It is questionable that the sleep stage observed in these participants is truly what we would regard as sleep.

 

A typical sleep cycle. Researchers recorded hallucinations in stages 1 and 2. We normally dream in REM (rapid eye movement) sleep. Image credit to Sleep 1102.


Secondly, a success rate of 60% is hardly news to excite those wanting to perform dream extraction. The crude prediction is not an exact match of what someone is seeing (as you can see from the video above). The computer is able to recognise that you were seeing a building, but not that you were cleaning windows of your own house for example. It is clear that it will take some time to really enter the realms of dream-reading. The interpretation of this crude prediction is also hampered by the fact that the study was based on only 3 participants. It is not clear whether this result will scale up to the larger public.

Despite these limitations, what the researchers have done is remarkable. They have shown that these early sleep hallucinations create very similar patterns of activity in the brain to when we are awake. They have shown a relatively accurate way to decode this activity into what the subject is seeing. And they have opened up the possibility of studying the function and nature of sleep in more detail. But don’t worry; the Thought Police won’t be after you just yet.

 

By Oliver Freeman @ojfreeman

 

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News and Views: The Brain Activity Mapping Project – What’s the plan?

Posted on April 24, 2013 by thebrainbank

“If the human brain were so simple that we could understand it, we would be so simple that we couldn’t” – Dr. Emerson Pugh

Isabelle Abbey:

An ambitious project intended to unlock the inscrutable mysteries of nerve cell interactions in the brain is on its way. Labelled America’s ‘next big thing’ in neuroscience research, the ‘BRAIN’ (Brain Research through Advancing Innovative Neurotechnologies) initiative will use highly advanced technologies in an attempt to map the wiring of the human brain.

Cajal drew some of the billions of neurons in the human cortex..technology has come a long way since 1899

Also referred to as the ‘Brain Activity Map’ Project (BAM), the BRAIN initiative aims to decode the tens of thousands of connections between each of the ~86 billion neurones that form the basis of human brain. Scientists believe completing the map will be an invaluable step that may have huge implications for therapeutically tackling neurological pathology.

Moving forward in this manner does seem particularly appropriate. For the past 10 years, we have been reaping the benefits of technologies like fMRI and PET scanning, which have allowed us to visualize the brain in a way that has never been done before. From measuring behaviours to diagnosing abnormalities, the contribution of neuroimaging to our understanding of brain physiology and pathology is undeniable.

Paul Alivastos, the lead author of the paper detailing the BAM proposal, aims to develop novel toolkits that can simultaneously record the activities of billions of the cells in the live brain, rather than from macroscopic slices. Eventually, these technologies will allow for the accurate depiction of the flow of information in the human brain, and how this may differ in pathological states such as in Alzheimer’s or autism.

Despite the daunting nature of the task at hand, this proposal has been met with much political enthusiasm. On 2nd April Barack Obama announced the American Government would be backing the project by approving a $100m funding budget for its first year of operation.

The humble nematode worm, 1mm long

But might this project need some grounding? After all, Alivastos and his co-authors are yet to establish the basis for which such tools can be developed or the extent to which these technologies could be used. The years of extensive research that has concentrated on mapping the wiring of a simple nematode worm, consisting of only several hundred nervous system cells, is yet to allow us to accurately predict the worm’s behaviour. So, some scepticism does seem reasonable.

While we must be cautious in predicting ambitious benefits from such a project, the map Alivastos and his colleagues have envisaged gives reason enough to be hopeful for the next decade in our neuroscientific appreciation of human cognition.

Natasha Bray:

As a neuroscience researcher, I can’t help but take an interest in the BRAIN initiative proposed by President Obama earlier this month. It’s a massive pot of cash designed not only to further the neuroscientific knowledge base, but also to create jobs and technologies that can’t even be described yet. As Izzy mentions above, the project is an ambitious and important undertaking that merits the now fashionable label of ‘big science’.

The BRAIN initiative is funded by a big pot of money from different resources including DARPA (the Defence Advanced Research Projects Agency), the National Science Foundation, the National Institute for Health, Google and various other institutes and charities.

So far, even defining the project and choosing suitable methods has been a challenge. The research leaders have proposed “to record every action potential from every neuron within a circuit”. Bear in mind action potentials (nerve impulses) happen in a matter of a couple of thousandths of a second, while a single circuit may encompass many millions of cells. At the moment, neuroscientists can record action potentials from up to about 100 cells simultaneously. We can work out anatomical circuits. We just can’t record from every cell within them; there is not one single tool in neuroscience’s toolbox that is currently capable of gathering that kind of data (yet).

There are, however, candidate techniques that could be improved or perhaps combined. Imaging techniques, including optical, calcium or voltage imaging, or magnetic imaging such as fMRI and MEG can scan on different scales in both time and space. Neurons’ electrical activity can be recorded using silicon-based nanoprobes or very tightly-spaced electrodes. Researchers have even suggested synthesising DNA that records action potentials as errors in the DNA strand like a ticker tape. Advances in all these technologies are still being made, making them the most likely candidates.

Added to the difficult choice of method is the serious task of storing and analysing quadrillions of bytes of data, plus the fact that it’ll take about ten years just to complete an activity map of the fly brain. It’s clear there are significant hurdles to jump. Then again, no one said big science would be easy…or cheap. But the potential benefits of big science are huge. The Human Genome Project had a projected cost of $3 billion, but was completed within its budget and has already proved a huge investment both intellectually and financially. It’s famously estimated that for every dollar originally invested in the Human Genome Project, an economic return of $140 has already been made.

I see the BRAIN initiative as a very worthy cause, a good example of aspirational ‘big science’ and a great endorsement for future neuroscience. One gripe I have with it, however, is that it seems a little like Obama’s catch-up effort in response to Europe’s Human Brain Project (HBP). The HBP involves 80 institutions striving towards creating a complex computer infrastructure powerful enough to mimic the human brain, right down to the molecular level. Which begs the question: surely in order to build an artificial brain you need to understand how it’s put together in the first place? I really hope that the BRAIN initiative and Human Brain Project put their ‘heads together’ to help each other in untangling the complex workings of the brain.

Posted in Isabelle Abbey-Vital, Natasha Bray, News and Views | Leave a comment

Preventing mitochondrial disease: Can three (parents) be the magic number?

Posted on April 22, 2013 by thebrainbank

Since September 2012, there has been a consultation in the UK on whether to allow the creation of three-person embryos. This may sound like an odd debate to be having, but there is a good reason for trialling this technique: to reduce the risk of genetic mitochondrial disease.

What are mitochondria?

Mitochondria

Often referred to as the “generators” or “batteries” of a cell, mitochondria provide the energy required for the cell to work normally. Each mitochondrion is tiny, only about 1 μM (1 thousandth of a millimetre) long, but their function is essential. Several mitochondria are found in each cell – the higher the energy requirements of the cell, the higher the number of mitochondria found there.

The curious thing about mitochondria is that they have their own little set of DNA. This DNA is responsible for the production of the building blocks that make up oxidative enzymes – proteins which are important for energy generation. Mitochondrial DNA consists of 16,569 base pairs, a tiny fraction of the 3.3 billion base pairs found in the nuclear genome.

Mitochondria have many unique features not found in any other part of the cell. Their DNA is circular – this is a feature normally found in bacterial cells (also known as “prokaryotic” cells), whereas humans and other animals store their DNA as strands in the nucleus (these are called “eukaryotic” cells). Mitochondria also have their own unique set of ribosomes, the machines which make proteins in the cell.

Pikachu

These distinctions have led scientists to theorise that mitochondria may have a different origin to the rest of the components in a cell. It is thought that they were once free-living organisms, something like bacteria. A long time ago, in the early days of evolution, these bacteria invaded an early incarnation of a cell. Both bacteria and the cell were able to co-exist perfectly together – the cell provided the bacteria with essential proteins and the bacteria were able to generate plenty of energy which the cell could use. It’s a bit like if your house was invaded by Pikachu – he would provide you with free electricity as long as you kept him well-fed. Both of you would benefit from the arrangement.

As this partnership worked so well, the bacteria were eventually assimilated into the cell and became a permanent feature. This is known as endosymbiosis – a mutually beneficial co-development of host and invader.

Mitochondrial Disease

Mitochondrial disease affects each sufferer differently. The affected mitochondria may only be in one tissue type or they could be in several. The most commonly affected organs include the brain, muscle and kidneys, because these require a lot of energy. There is a huge variety of symptoms, making it very hard to diagnose. Some types of mitochondrial disease have more common symptoms and so are termed under collective names –such as Alpers’ Disease and Leigh Syndrome. The onset is usually in childhood but it can also develop in adults. About 4000 children a year in the US are affected by mitochondrial disease and in severe cases it is fatal, with the child unlikely to reach adulthood. So far, there is no known cure.

Three-person embryos

Every embryo contains three separate genetic components: DNA from the father, DNA from the mother and mitochondrial DNA. These are brought together when an egg cell, containing both maternal and mitochondrial DNA, fuses with a sperm cell containing paternal DNA. In cases of mitochondrial disease, the mitochondrial DNA in the egg cell is damaged, and this damage can be passed on to the child who may then develop disease symptoms. By creating three-person embryos, scientists are hoping to prevent mitochondrial disease by replacing the faulty mitochondria with normal ones before the embryo develops.

There are two techniques to create three person embryos which are being discussed. The first is called “maternal spindle transfer”. The idea behind this is to take an egg from the mother and remove the nucleus containing all of her genetic material apart from the mitochondrial DNA. A donor egg with healthy mitochondria has its nucleus removed and replaced with the nucleus from the mother’s egg. The egg will then be fertilised by the father’s sperm, in a similar way to conventional IVF.

The maternal spindle transfer technique has been successful in animal trials. In human trials however, only about half the eggs made using this technique developed normally. The researchers involved still think the results are encouraging enough that the technique should be allowed to go the next stage: clinical trials. Currently, this is illegal in both the US and the UK. The present government debate is whether to change the law to allow these clinical trials to occur.

The second technique is called “pro-nuclear transfer” and involves fertilising both the mother’s and donor’s eggs with the father’s sperm. Before the eggs divide, the nucleus is removed from both eggs, and the nucleus from the mother’s egg is placed in the donor’s. Doug Turnbull and his team at Newcastle University in the UK have pioneered this technique and have successfully developed embryos to about 100 cells (the “blastocyst” stage).

A mother, a father and a little bit extra

Mitochondria contribute only a tiny amount of the DNA to a person’s genome. Therefore, a three-person embryo would consist mostly of the DNA from the father and mother, with only a small proportion coming from the donated mitochondria.

Mitochondrial genomeThere is much controversy surrounding “three-person embryos”. For starters, the phrase itself sounds a bit weird and unnatural. What’s more, there are multiple ethical issues and moral arguments, such as “interfering with nature” or who will have parental rights. Some people are worried about what impact having three genetic parents would have on a child’s development. Others point out that this won’t cure existing sufferers; it would just prevent new babies from being born with the disease. Furthermore, it is not known what effect this technique could have on future generations.

However, the concept of “three parents” is not as bad as it sounds. The tiny mitochondrial genome is only responsible for certain basic processes. So, it appears unlikely that having the mitochondria from another person will have a big impact on the development of the characteristics of the embryo or the child, such as its appearance or personality.

It may be possible to reduce any “three-parent” risks by using mitochondria from a family member of the father. The mitochondrial genome is always inherited from the mother, as mitochondria are present in the egg at fertilisation. In the same way, the father’s mitochondria will have been inherited from his own mother. Donation of an egg from a maternal relative of the father (his mother, a sister or maternal aunt) would ensure the embryo would still inherit the exact mitochondrial DNA of one parent, in this case, the father rather than the mother.

The concepts and techniques behind mitochondrial donation have been subjected to ethical reviews, which concluded that the techniques are promising but that more research is needed. However, doing further research would require a change in the current law as genetic modification has never been tried to this extent in humans.

The future of mitochondrial donation

The Human Fertilisation and Embryology Authority (HFEA) have been consulting public opinion of three-parent embryos. They published their results in March 2013, finding that 44% of the 1000 people surveyed approved of the technique, with 29% against it. However, an open online questionnaire found that 455 people were in favour with 502 against. So, public opinion is clearly divided on the issue.

I think the term “three-person embryos” or “three-parent babies” should be dropped because it has alarming connotations, making the technique sound strange and unnatural – a bit like the “Frankenfood” label given to GM crops. Describing it as “mitochondrial donation” may encourage people to understand its potential benefits and may help dispel controversy. The very existence of mitochondria in our own cells proves that something that seems unnatural can be benign or even beneficial – if those proto-bacteria hadn’t invaded the host cells all those millions of years ago, life as we know it would never have developed in the first place.

The UK has always been at the forefront of scientific innovation, especially with fertility. This was highlighted by the recent passing of Sir Robert Edwards, one of the scientists who pioneered the IVF technique (unfortunately his death in April 2013 was somewhat overshadowed). His legacy was to bring desperately wanted children into the world, and now we have a chance to improve on that by adapting his technique to reduce suffering. I sincerely hope the government gives the green light to further investigate this concept. Of course, lots of work still needs to be done before the technique can actually be used, if it can be used at all. However, I think the researchers should be given the opportunity to develop this potentially life-saving technique.

Post by: Louise Walker

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News and Views: The Festival of Neuroscience – A 5 minute guide.

Posted on April 14, 2013 by thebrainbank

BNA

 

Between 7th-10th April 2013, neuroscientists from across the globe met in London for the British Neuroscience Association’s ‘Festival of Neuroscience’. Here is my whistle-stop tour of the main talking points.

 

 

Drugs, neuroscience and society

Instigated by the divisive Professor David Nutt, delegates heard about research into cognitive enhancing drugs. Professor Judy Illes suggested these drugs should be labelled ‘neuro-enablers’ not ‘neuro-enhancers’ to focus on their role in improving cognition in those affected by diseases such as Down’s syndrome. Topics debated included: Should we criminalise use in healthy people?; Should we allow their use in exams, job interviews etc.?; Should we allow them only if declaration of use were compulsory?; Would this lead to two-tiered exams – users and non-users?

 

Dr Paul Howard-Jones spoke of ‘neuromyths’ in education. He highlighted the oft-cited theory that children all have their own learning style (visual, kinaesthetic, auditory etc.) as having no scientific basis. ‘Neuromyths’ are routine in the field of education, he said.

 

Professor Emeritus Nicholas Mackintosh described findings in the Royal Society’s report into neuroscience and the law. Bottom-line is that there is very little evidence thus far to suggest one can use brain scans successfully in a court of law. Only once has neuroscience been used successfully in court.

 

Pain, placebo and consciousness

Professor Irene Tracey gave a fantastic plenary talk on imaging pain in the brain. She gave wonderful insights into how the placebo effect is very real and can be seen in the brain. A placebo can hijack the same systems of the brain that (some) painkillers act on. This could have strong implications for the experimental painkiller vs. placebo set-up of randomised controlled trials.

 

Professor Ed Bullmore spoke about the connectivity of the brain. He described the intricate connections of the brain and how some regions are highly connected whilst others have only sparse connections. He noted that in a coma, highly connected regions lose connectivity and sparsely connected regions gain connectivity. This goes nicely with the work by Giulio Tononi into theories of consciousness.

 

Professor Yves Agid entertained with his animated talk on subconsciousness. He argued that the basal ganglia are crucial for subconscious behaviours. He showed that the basal ganglia become dysfunctional in diseases such as Tourette’s syndrome and Parkinson’s disease – both of which involve defective subconsciousness.

 

Great science

Professor David Attwell told a wonderful story about glia, the support cells of the brain. Glia are often forgotten about when talking about functions of the brain, but Prof Attwell described fantastic research condemning this. Glia are involved in brain activity, both in health and disease. Glia are involved in regulating the speed of nerve cell communication. Glia may also be involved in learning and memory.

 

Professor Tim Bliss, one of the pioneers of research into memory formation, spoke about his seminal discovery of long-term potentiation. He recalled the story behind how he and his colleague Terje Lømo discovered one of the mechanisms that mammals use to store long-term memories. He even owned up to falling asleep during the published night-time experiment and failing to jot down the data for a short period! #overlyhonestmethods

 

Professor Anders Björklund gave a public lecture on his life’s work into stem cell therapy to treat Parkinson’s disease. He showed some wonderful results that have really made a difference to patients’ lives. This therapy shows good improvement in ~40% of cases. Work continues into why it does not work in all cases.

 

To follow what else was said during the conference, see #BNAneurofest.

 

By Oliver Freeman @ojfreeman

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