Optogenetics in Humans?

Just over 10 years ago marks the development of one of the most important tools in recent neuroscience history – optogenetics. To put it simply, optogenetics is the process of using light to activate cells (generally neurons) by implanting light sensitive proteins known as opsins, which will then cause firing of the neuron when activated by light.

Obviously activating neurons is nothing new, scientists have been using electric currents and pharmacological interventions to stimulate neurons for years. But the discovery of optogenetics led to many more exciting prospects; firstly the ability to target specific neurons – something electrical stimulation lacks is spatial sensitivity which can lead to unwanted side effects when neurons other than the target cells are stimulated. Optogenetics also allows for neurons to be activated on a much more sensitive timescale – this is in comparison to drugs which can take from minutes to hours to finish exerting their effects.

Like every new technique optogenetics wasn’t without its problems for the first few years, and many scientists that have attempted to use it have failed. However there has been some pretty incredible science out of this discovery that wouldn’t be unheard of in science fiction, such as the implantation of false memories in mice (original research paper found here), and the ability to reactivate otherwise irretrievable memories (original paper here). Memory is a research area that has particularly benefited from the discovery of optogenetics, as it allows for reversible activation/inactivation of certain brain regions. Reversible being the key word here – much of our initial knowledge on memory came from research using lesions of specific brain areas to examine how this can affect memory, and while lesion research has taught us a vast amount, the ability to reversibly activate/inactivate a specific area of the brain can teach us so much more.

Of course as with any technique, once animal studies using optogenetics started showing success, many began to speculate on the use of optogenetics in humans, however this isn’t without its difficulties. One of the biggest obstacles would be the actual delivery of opsins into the neurons. In animal models we usually use genetic manipulations which are not possible in humans. Viral delivery is another option however this can create problems such as overexpression and could also elicit immune responses as the gene products being delivered would be from other species. We also need to develop methods to measure opsin expression in humans, as generally in animal models this is done post-mortem.

Despite these problems, many believe that one of the most likely clinical applications for optogenetics is Parkinson’s disease. Currently deep brain stimulation can be used to alleviate some of the symptoms of Parkinson’s– this involves electrical stimulation through a small electrode implanted in the brain. However this method has problems with spatial and cell specificity and can therefore lead to the stimulation of healthy brain cells and therefore unwanted side effects. These side effects could be overcome with the use of optogenetics to increase spatial sensitivity. However, one of the major problems concerning this application is that this does not treat the underlying cause of Parkinson’s, only alleviates the symptoms. Other drug treatments treating the symptoms of Parkinson’s have been found to lose effectiveness over time – could this be the same for optogenetics?

Another exciting, and perhaps more feasible application of optogenetics is in the treatment of blindness in humans. In fact clinical trials have now been approved in humans to use optogenetic techniques to help restore photo-sensitivity to those suffering from a form of blindness known as retinitis pigmentosa. The outcome of these clinical trials could prove that as well as tool for studying brain mechanisms in animal models, optogenetic techniques could also hold potential as a therapeutic tool for humans.

Overall I believe that optogenetics as a technique is still in its infancy, and the extent of knowledge to be gained from this tool is yet to be fully realised. Although the use of optogenetics in humans may be overly optimistic, there’s no denying that it’s a fascinating tool that has changed the face of neuroscience research.

Exercise and Obesity -Problems with Science and the Media

There’s no shying away from it, we are in the midst of an obesity epidemic. More people are overweight and obese than ever before, so obviously ‘how to lose weight’ is currently a bit of a hot topic in the media. When it comes to losing weight the first option for many is often an alteration in diet and/or an increase in exercise. Logically thinking, exercise alone should lead to weight loss. Exercise burns calories, and if you burn off more calories than you take in you will lose weight. But typically life could never be that simple. Recently a paper was published called ‘Constrained total energy expenditure and metabolic adaptation to physical activity in adult humans’ (us scientists love a good snappy title), hinting that the relationship between exercise and weight loss may not be as straight forward as it seems…

Cue a media frenzy including headlines such as ‘Exercise does not promote weight loss…’ and ‘Scientists: exercise doesn’t help you lose weight’. Well that sounds great thanks Daily Mail, in that case I think I’ll just go and sit on my sofa for a few hours and eat some cake instead of going for a run…

Obviously, as with many health stories in the media, the claims from this study have been wildly exaggerated. What the research actually says is that the relationship between energy expenditure and exercise is not a simple as first thought – when doing high levels of exercise, energy expenditure from a range of other physiological processes may be decreased, therefore leading to a lower overall energy expenditure than would be expected was the relationship linear. In other words, the body reaches a ‘plateau’ where increasing exercise levels does not necessarily mean burning more calories. While this is of course a very interesting finding, it is in no way claiming that exercise can’t help you lose weight.

Of course there are many problems with using exercise alone as a tool for weight loss. Firstly, in order to be effective in inducing weight loss, diet must remain the same (assuming consumption of the same number of calories as would usually be expended, which very rarely happens). This can be very difficult as exercise stimulates appetite, and can therefore lead to a higher consumption of calories than normal, thereby eliminating the calorie deficit that the exercise has created. Furthermore there is evidence to show that often when people do exercise they can become ‘lazier’ in other aspects of their life. For example, after going to the gym I might decide to take the lift instead of the stairs as I’ve already done enough physical hard work for the day – enough small changes like this can again lead to an elimination of the calorie deficit created by the exercise.

However in many cases the opposite might be true. For some people the psychology of doing exercise may generate a positive frame of mind whereby they won’t have that cheeky bit of chocolate as it would undo all of their good work. Adding to this exercise has been shown effective at improving mood and therefore may help to reduce the calories usually consumed through ‘comfort eating’.

Furthermore we mustn’t forget that even though exercise may no longer be considered as important for weight loss as it once was, its other numerous health benefits cannot be ignored, and headlines suggesting that exercise may be pointless are incredibly dangerous in a society where lack of physical activity is already a large problem.

Could it be that these media stories may encourage more extreme dieting? After all if exercise doesn’t aid weight loss it would probably be considered easier to simply diet – and let’s face it, in today’s society there are plenty of ‘fad’ diets to choose from, all based on supposedly sound advice from so-called ‘nutritionists’. And while it’s overwhelmingly clear that obesity is on the rise, we mustn’t forget about eating disorders such as anorexia which are also on the increase, and encouraging people to live off cabbage soup and smoothies certainly isn’t a healthy or sustainable way of losing weight/creating a healthy relationship with food. While these diets are often successful in the short term, there’s a lot of evidence to show that diets rarely lead to long term weight loss and within a few years most dieters are either back to their original weight or heavier. In fact the only treatment for obesity that has shown long term success is bariatric surgery, and scientists are still puzzling over the exact mechanisms behind this.

Just to add the never-ending saga of exercise and weight loss stories, recent research has now claimed that fitness gadgets such as Fitbits and Jawbones may also have no use in aiding weight loss. Clearly this may be true in some cases, however I for one resent the media using this research to disencourage the use of this sort of technology when in some cases it could help to promote a healthier lifestyle. After all health is not always defined by someone’s weight/ability to lose weight.

I could go on forever but I’ll end with this sentiment. Science is obviously incredibly important, however until there is a fair and true representation of scientific research in the media we run the risk of losing all public faith in research, as well as possibly promoting useless and unnecessary lifestyle changes that could lead to more problems in the long run.

 

 

Here’s a link to the original research paper for anyone interested in having a read:http://www.cell.com/current-biology/abstract/S0960-9822(15)01577-8

and here’s the one on wearable fitness gadgets:http://jama.jamanetwork.com/article.aspx?articleid=2553448