“What are all these chemicals for?” – aka, a very basic primer on Formulation Chemistry

Formulation Science?

I’m currently studying for a PhD in Chemistry, and yet never during my Chemistry Undergraduate or Postgraduate career have I come across any modules or even seminars touching on formulation science. This is largely because formulation science is seen as an industry staple, something that doesn’t have a place in more blue-sky, academic research such as university is geared towards. Formulation, outside of industry, is considered more something that a good chemist will be able to pick up on the job.

And yet, it is an absolutely crucial discipline. Formulation scientists do exactly what you might expect from the name: formulate the complex mix of chemicals that makes up a tablet, powder, aerosol, gel, cream (etc.). Without them we wouldn’t have shampoos, deodrants, paints, medicines and even some foods.

But why all the chemicals?

Funny how you might ask that, reader, but everything is made up of chemicals. Foods found in nature actually have a colossal number of different chemicals in them. This is because a very delicate balance is required to maintain a stable, pallatable formulation.


Having a mix of chemicals means you can more finely tune the properties of a particular substance. Think of it like a carrot cake.

Formulating a Carrot Cake

In all cakes, you need butter, margarine or oil to lubricate the mixture and enhance the texture of the finished product. For a carrot cake, you also need self-raising flour and baking powder. Proteins within the flour form a network of gluten when mixed with moisture, which allows the cake to rise. Baking powder creates bubbles of air in the mixture which enhances this rise.

To enhance the flavour of our carrot cake, we also add in some cinnamon, nutmeg and ginger. Sugar also enhances the sweet flavour of the cake – but in addition it absorbs moisture from the mix and thus avoids the cake from getting too hard.

Carrots and orange zest are also needed to tune the flavour of the cake (the former giving the cake its name, after all). However, these ingredients also add moisture to the mix that it would not have otherwise. The quantities of the other ingredients must thus be altered to allow for the inclusion of the wet fruit and vegetables to stop the final product being too dense.

Last but certainly not least: eggs. Eggs are an emulsifier, meaning they can help in the combining of oily and watery mixtures. In cake, they help to combine the liquid and solid ingredients into an even mix. And this is even without thinking about the icing!


So you see, it is essential to consider the exact properties you need for your final product, and to tailor the ingredients to ensure you achieve this. I’ve found that chemists are well-suited to baking for precisely this reason: they appreciate the complexity and intricacy of a good formulation.



(1) An excellent online resource on cosmetic chemistry, which is a form of formulation science.

(2) The RSC subgroups pages on formulation.

(3) Article showing three naturally occurring foods’ chemical “ingredients list”.

Problems in Pharmacology: The Unexpecting Guinea Pigs


Clinical trials are the bane of doctors and researchers alike. They are expensive, they rarely pay off, and they take a long time. But of course no one wants a situation where we simply don’t test drugs before we give them to vulnerable patients. The consequences of under-testing are dire, and it still happens that drugs get withdrawn (as a case study, have a look at Benfluorex’s staggered withdrawal in the EU).

Much as it is clear that drug trials are essential before their widespread introduction to a hospital drugs chart, it is also clear that there are risks involved.

On Clinical Trials

The clinical trial process goes something like this:

  • Several months testing in up to 100 healthy volunteers to assess its safety and appropriate dosage (though the latter will vary depending on the patients’ condition).
  • Up to 2 years testing in a few hundred patients with the disease of interest to assess efficacy against the disease and side-effects.
  • Several years’ testing in up to 3000 individuals with the disease of interest to further assess efficacy and side-effects.
  • There may then be a 4th phase of testing to further assess the safety and side-effects if not enough is known.

There are several reasons why clinical trials are expensive, why they fail, why they take so long – these are things I could easily spend a whole post discussing. What we are talking about here is just SAFETY.

waiting-room-1631142So why is it that, after a whole clinical trial, things can still go wrong?

My favourite word to describe patients is “idiosyncratic”. And it fits perfectly here. Patients are idiosyncratic, different, individuals. They have different bodies, different organs, different cells, different DNA, and therefore their reaction to a chemical being ingested or injected is going to differ from another person.

Sure, we can look at measurable variables such as age, height and weight and predict how these affect a patient’s response to a drug. We can even sequence someone’s DNA and look for heritable characteristics that predict a response as well. But there’s an infinite number of non-heritable characteristics, and non-nuclear DNA to account for as well.

So why do we use drug trials, if they’re so very useless? Simply put, it’s the best thing we have. With novel gene-sequencing technology available to us, we may be able to streamline the process quite a lot in the future, but it’s likely to still be imperfect. Especially as so many life-threatening disorders and diseases only manifest themselves beyond the point of no return.


Who are the guinea pigs?

At the beginning of the year, the Independent published an article about the three most recent drug trials that led to devastating consequences for the volunteers. I’ll link it here as a summary of what can go wrong for the guinea pigs choosing to participate in drug trials.

Other than these participants, there are two other groups that effectively are treated as guinea pigs: children and pregnant women.

baby-hand-1-1316351It is precisely due to the risks outlined above that we do not include the “at risk” groups of children and pregnant women in clinical trials. Side-effects that could be a minor inconvenience in a healthy individual are exacerbated drastically in unborn children and young people as they could effect their development.

This means that a paediatrician must rely on their expertise and experience alone to prescribe adult-tested medicines on children: tailoring the dosage to the child’s height and weight. As explained above, this isn’t enough. As adult patients’ bodies are idiosyncratic, a child’s body is an entirely different matter. There are countless chemicals running around that we don’t see in an adult, that may interact with the ingested drug in an adverse way.

In addition to the difficulty in predicting side-effects, adherence to a medicine regime is also more tricky. Children don’t want to take in nasty-tasting drugs (I personally would only take sweet-tasting cough syrups), and they don’t want to have to take several at once (which may be necessary in combination therapy).



Pregnant women are also guinea pigs. This means that a gynaecologist must make the same judgement calls as a paediatrician must with children, and these choices affect not only the pregnant woman but their unborn child as well.

As stated many times in this post, it is difficult to predict the activity of a drug in an individual. It is especially difficult to predict the activity of a drug in an individual who has not yet been born. In particular, it would be useful to know just how much of the drug is sequestered by the fetus. The mother and child have a semi-permeable barrier maintaining the separation of their blood systems. As with the testing of a drug’s ability to cross the blood-brain barrier, we need to know how much of the drug crosses this membrane in the placenta to know how much will be taken in by the unborn child.


This lack of knowledge leads to doctors estimating the appropriate usage of a drug. In fact, it is not unheard of for doctors to prescribe a drug to a pregnant woman for off-label purposes (ie. for purposes other than it has been tested for).

Thalidomide is a terrifying word in chemistry. It has come up in my education separately at least half a dozen times, and with good reason. If you need to brush up, have a look at this Wikipedia article or this article by the Science Museum. Notably, this is a case in which a drug used for morning sickness led to teratogenic effects in unborn children (ie. birth defects).

Inside their mother’s body, the fetus grows from a single cell to form a full baby. This process follows a delicate series of chemical signals within the developing child to ensure that the baby is born fully formed. It therefore follows that anything affecting the chemical environment the developing child is subjected to will have an effect on its development.

The Bottom Line

We need to somehow safeguard child or pregnant patients against preventable adverse effects. There are indeed clinical trials involving children in existence.

We know that clinical testing has an inherent risk, but we do it anyway because the risk in a clinical trial is far lower than going without. That is why it makes sense to test (with due care) in these vulnerable patient groups.

So why are we still lacking data? Unfortunately the issue comes down largely to funding. As with infectious disease drug trials lacking momentum due to less chance for profit from poorer countries, trials that have smaller target patient populations are less common because the final drug brings in less money. There’s less financial incentive to offer trials just for these select patient groups.

The cynic’s bottom line: we need to encourage funding in trials in these essential patient groups!




  1. European Medicines Agency document recommending Benfluorex withdrawal.
  2. Chemistry world article on Benfluorex.
  3. The FDA’s site on the Drug Development Process: Clinical Rsesearch.
  4. The Independent’s article “The troubled history of clinical drug trials”.
  5. Page on placental transport.
  6. Thalidomide articles: 1, 2.
  7. WHO page on Clinical trials in children.
  8. NIH page on Clinical trials in children.

Images used: 12, 3

Life Span: The World’s Longest Cohort Studies

This post is inspired by my recent visit to Hiroshima in Japan. Whilst there, I had the chance to visit the Peace Park and Peace Museum. Unfortunately, the latter was under refurbishment at the time, and therefore only half of it was open. The museum did, however, provide incredibly valuable and poignant insight into the effects of the bomb on the citizens of the city. When we visited, it seemed that the exhibits focused only on the detonation and aftermath, and did not encompass the context behind the bombing at all. Presumably, this will be addressed by the renovations.

Little Boy

On the 6th of August, 1945, at 08.15 AM a “Little Boy” atomic bomb was dropped above Hiroshima. It was detonated 580 m above the city, directly above Shima Surgical Clinic. Almost 150,ooo people in total were killed or injured by the bomb.


Sadako Sasaki was two years old when the atomic bomb struck 2 km from her home. She was seemingly uninjured by the blast or aftermath. However, at the age of 11, she developed cancerous swellings around her glands. These swellings led to a diagnosis of acute malignant lymph gland leukemia.

There is a Japanese myth that promises a wish to anyone who makes 1,000 origami cranes. By the end of August 1955, Sadako had made more than 1,000 cranes, wishing that she could survive her cancer. By the end of October, she had died. Sadoko’s death led to the building of a memorial for all children who had died from the effects of the bomb.

Long-term Radiation Effects

Sadoko’s story led to further research interest into the long-term effects of radiation. Because people were exposed to the radiation in different forms, the effects manifested in different ways. The long term effects of the atomic bomb included blood disorders such as anemia, cataracts, tumours and keloid scarring around healed burns. As these long term effects were not previously explored, it was not possible to predict them.

crane-1403798There are several kinds of radiation. Alpha and beta radiation do not have high penetrating power – that is, when they reach the skin, they cannot pass through and therefore do not affect the internal vital organs. These kinds of radiation cause skin effects such as burns, or can have wider effects if ingested as contaminated water or food. Gamma and neutron radiation have a high penetrating power, and therefore pass through the skin. Because of this, full body exposure to gamma radiation leads to the symptoms of radiation sickness (nausea and vomiting, falling blood counts, infection).

As the effects of radiation were not widely known, it is likely that many of the aftereffects of the bomb were caused by contamination of the water supply or exposure to “black rain”. These symptoms in particular are associated with radiation sickness due to the internal effects of radiation. Radiation damages DNA and other molecular machinery within the cell. This means that the symptoms are linked to newly synthesized cells, and they manifest most quickly in rapidly-dividing tissues (hair, blood, skin).

The Study

This bomb was the first of its kind to be used in warfare, and no one could fully predict the long term consequences for those surviving the initial blast. The Atomic Bomb Casualty Commission (ABCC) was established in order to conduct long term studies of those survivors. This commission later became the Radiation Effects Research Foundation (RERF), and the study findings can all be found on their website.

These studies are incredibly valuable in understanding the different conditions in which radiation exposure plays a part. Through the voluntary cooperation of tens of thousands of survivors, we have learnt that cancers have higher incidence in A-bomb survivors. There was no evidence of an increase in other mortalities than cancer in the group – presumably because cancer is the disease that specifically stems from damage to DNA and other growth/death mechanisms in the cell (which is specifically what radiation causes).

From an academic point of view, the existence of such a long-spanning study is extraordinary, and it has value beyond its “limited” purpose of studying A-bomb victims. If we followed other patient groups for a life span, we could learn so much about both inherited and environmental factors’ roles in any disease.

We could look at the effects of diet on brain cancer. We could look at the effects of exercise on. Previously unstudied connections could potentially be found. And most of all, we would be able to know these things in healthy individuals, not just those suffering from the disease already.



  1. Hiroshima Peace Museum website, accessed 30/08/16: http://www.pcf.city.hiroshima.jp/index_e2.html
  2. Sadako Sasaki, accessed 30/08/16: http://www.pcf.city.hiroshima.jp/virtual/VirtualMuseum_e/exhibit_e/exh0107_e/exh01071_e.html 
  3. Atomic Archive website, accessed 30/08/16: http://www.atomicarchive.com/Effects/effects16.shtml
  4. RERF website, accessed 30/08/16: http://www.rerf.jp/library/archives_e/lsstitle.html
  5. Crane photo taken from: http://www.freeimages.com/photo/crane-1403798

“Expanding” our biological universe


I recently (well, fairly recently) gave a presentation in my research group on this topic. Both microscopy and polymer synthesis are sciences close to my heart, so I thought it was worth attempting to explain the science to a wider audience. Please do have a look at the paper or Science Mag. article if you’re interested in learning more. My original presentation took a more in-depth look at the science, but I felt this was not appropriate for a blog post.

Microscopy: Biology’s teeny tiny little camera

Microscopy is a hugely valuable technique in many fields, not least biology. Using microscopy, we have access to high-quality images of structures we could not see by eye, and this allows us to visualise the workings of organisms, cells and even sub-cellular processes.

Microscopy has led to so many key discoveries such as the cell, which was discovered by Hooke using an optical microscope, and it has contributed to and even won Nobel Prizes (such as in super-resolved fluorescence microscopy in 2014).

The issue with optical microscopy

The oldest form of microscope is the optical microscope. These are microscopes using a complex series of lenses to magnify an image. And the higher resolution optical microscopes are termed confocal microscopes. These are able to takes images through z-planes (they take “stacks” of 2D images and show them to the user as a 3D image) and videos of subcellular structures.


This is where it gets a little complex (apologies). See, there is a problem with typical optical microscopes. Their resolution (that is, the quality of the images, and their ability to zoom in further) is limited by diffraction. Visible light passing through the microscope’s aperture (the hole where light passes through) undergoes diffraction, and this means that two objects separated on a 2D surface (laterally) less than approximately half the wavelength of light used to image the specimen cannot be observed.

SO how do we surpass this limit? Having higher resolutions for our images is ever more important as we learn more about how our cells work. Neurons (brain cells) are notoriously small, for example. Non-optical microscopy techniques are tricky to implement with living tissue as they can damage it. There are, however, expensive “superresolution” microscopes that can break this “diffraction limit”. I’m now going to show you a technique that bypasses the expense and the damage to cells published in the Journal Science.

The solution: “Expansion Microscopy”

An entirely alternative solution to the above issue is to expand up the living tissue to be able to visualise it with a lower-powered microscope. In the Science paper, the researchers infused starting materials for the preparation of a polymer directly into the tissue. They then added a crosslinker to allow the formation of a web of polymer, and chemicals to initiate the formation of the polymer in the tissue. Infusing water into the polymer web (termed dialysis) encouraged it to swell, in the same way that nappies swell when absorbing moisture.




Using typical techniques for labelling their samples (confocal microscopy requires fluorescent dyes to visualise specimens), the researchers found their samples to be undistorted, and 4.5 times larger than the original tissue. In this way, the technique showed the ability to visualise samples with the same resolution as superresolution microscopes!

This sort of lateral thinking is a wonderful thing in modern science, as much of the research we do these days is based on what is funded by industry. Keep it coming, scientists!

A note from the author: As my posts sometimes touch on emotive subjects, comments are disabled after 14 days. This is because, at this stage, I feel that ongoing discussions tend to stagnate.




Science Mag. article

  1. Chen, F., Tillberg, P. W. and Boyden, E. S. (2015) Expansion microscopy. Science Translational Medicine. 346, 6221, 543-548.

Image of diapers was taken from freeimages.com

Five shorter (political) stories: 2


The UK is a worrying place to live at the moment, with soothsayers preaching about economic, social and environmental collapse at every street corner (or posting about it on Facebook, at least). This makes it a perfect time to post a few stories about factors leading to political persuasion! In science we trust.

Research by various political scientists has suggested that around half of the variation in political preference is heritable (that is, determined by our genetic makeup). In this post, I’ll be talking about non-heritable (that is, social and lifestyle) factors that affect political persuasion.

Birth order

It may well affect political persuasion. There have been various studies suggesting the impact of birth order, including one in which parents’ social persuasion was not linked. Though it is difficult to ascertain why, it has been suggested that this is due to the “dominance hierarchy in the sibling relationship”. It is suggested that being the first born fosters a sense of privilege that leads the offspring to swing towards favouring the “political status quo”.

Siblings and stereotypes

Men raised with sisters tended to be more conservative according to a recent study. This has been proposed to be related to the attitudes related to gender roles instilled from a young age. Boys with sisters will see their sisters encouraged to engage in household chores and more “girly” pastimes (toys are still very gender segregated to this present day, though attitudes seem to be changing gradually). This early gender stereotyping may translate into more stereotyped roles, again maintaining the status quo, in later life.

Conversely, growing up with a sister had no effect on young girls. In addition, the study has suggested that the effect decreases as the young men grow up. Unfortunately (though not related to this story), the data did show the persistence of gender stereotypes for longer.

Personality profiling

A study has suggested that political persuasion can be predicted as a function of 5 personality traits: Openness, Conscientiousness, Emotional Stability, Extraversion and Agreeableness.

Openness and Conscientiousness were found to be the best predictors, with more of the former correlating to conservatism and more of the latter correlating with more liberal attitudes. The other traits varied more, though Emotional Stability and Extraversion had moderate links to social conservatism but more effect on economic persuasion. Agreeableness, conversely, was related to social conservatism by economic liberalism.

These data in particular suggested that politicians with certain values could have predictable views on an array of policy domains, which is supported by the relative cohesion within a political party relative to beyond.

Oxytocin: the “moral molecule”?

Oxytocin plays a role in social interaction, particularly during sexual reproduction and during and after childbirth. It has been shown to be related to the formation of monogamous pair bonds in humans and other species.

Research undertaken in the Center for Neuroeconomics Studies (CNS) in the US investigated the role of oxytocin in political persuasion. Synthetic oxytocin (or placebo) was administered to volunteers (not females due to its affect on the menstrual cycle) and they were asked about their feelings towards various political figures.

Those of a Democratic persuasion showed more warmth towards their opponents with than without oxytocin, whilst it had no effect on Republicans. This data suggested that those who lean more to the left are less fixed in their views and are more affected by their emotional response.

Voting participation and stress

Though not related to political persuasion, another hormone may have an affect on voter turnout.

A small study explored how cortisol (often dubbed “the stress hormone”) may have an effect on voting activity. Lower cortisol levels in the afternoon were associated with increased voting frequency, but not with non-voting political activity (such as campaining). Baseline cortisol levels predicted behaviour that was not affected by demographics.

Cortisol is a hormone that can also predict participating in social interactions. The paper’s authors note that, as political activity is a stressful undertaking, it makes sense that those with lower stress thresholds might avoid engaging.

The other factor most highly affecting voting turnout was age, with older people voting more often. This study suggested that hormone levels, as well as demographics, should be taken into consideration, however.


One thing to note is that much of this research is that it is based primarily on surveys conducted where participants self-report. Although participants have no reason to lie in such studies, there is always the chance. But data on these larger scales is likely to be fairly indicative, and statistics do not lie (most of the time).


A note from the author: As I sometimes write on emotive subjects, comments are disabled after 14 days. This is because ongoing discussions tend to stagnate.

Four shorter stories: 1


This blog exists as a canvas on which I paint my various musings on science and medicine (and some other things). Years of training does more than just make you able to interpret scientific findings – it makes you acutely aware of how much else there is out there to learn! But sometimes I don’t have enough to say on a particular subject to fill a full article, and that’s okay. This new feature (if it becomes a feature) is where I introduce some short stories that captured my interest, but I haven’t immediately found myself internally linking them to a wider context.

I present to you: the Amazon molly

Let’s start off this serious of short stories in the way we mean to go on, with a story about peculiar mating habits! I believe I read about this phenomenon a while ago in The Scientist magazine, and it stuck with me.

The name of the fish is a reference to the all-female Amazon warriors from Greek mythology for a reason: they reproduce by gynogenesis. This means that only the genetic material from the females of the species is incorporated into their offspring. The Amazon molly mates with a male of a fish from the same genus as itself (Poecilia), but the sperm is required only to initiate embryogenesis (the division of the egg to form a viable embryo).

Though it is interesting, this method of reproduction does limit the ability of the population to be genetically diverse. Two key sources of genetic variability in humans, for example, are from the crossing of chromosomes from two species in sexual reproduction and genetic mutations. The Amazon molly benefits only from the latter, but is able to reproduce faster. A smaller gene pool means that the Amazon molly is less able to adapt to changes in its environment such as disease or climate change.


Put Solar on it 

This is a project encouraging people to put solar panels on their homes, commercial building and lands to produce more renewable energy, and it had a national day in the US as a call to action.

Climate change has long been an issue for experts, scientists and politicians, but it’s time to change that. If we want to preserve out own earth we should consider making changes ourselves. Solar panels are now cheaper than ever before, and renewable energy has been proven to be a viable source for all our needs.


Wind farms and hurricanes

Another story from the US, and one I heard on Inquiring Minds podcast many moons ago.

Our power industry relies on the conversion of one type of energy being converted to another. Batteries are chemical energy converted to electrical energy, coal/gas are heat energy being converted to electrical energy and wind farms are kinetic energy being converted to electrical energy.

Energy is not just created, it is converted.

It therefore stands that, when we use wind power, we reduce the amount of wind evergy in the atmosphere. A study was carried out wherein it was stipulated that 78,000 turbines could have knocked down Hurricane Katrina and Hurricane Sandy. That’s a lot of free energy, and these turbines could actually save lives.

Does this change what we know about wind power? Well, no, but it might make people listen.

Is it feasible? There is no reason why not.


Project Steve

Finally, this is something I heard about on one of my many super fun Science Podcasts. Project Steve is a parody of the tendency of creationist organisations to list those who naysay evolution, amongst many things.

Quite simply, it is a sort of petition wherein scientists called Steve put their name down to support evolution. At the time of writing, 1389 Steves had signed – the website notes that ‘”Steves” are only about 1% of scientists’ to remind us all just how wrong the tradition is to frame certain scientific doctrines as “disputed”.


A note from the author: As I sometimes write on emotive subjects, comments are disabled after 14 days. This is because ongoing discussions tend to stagnate.

How anyone can be a Scientist


What is Citizen Science and why should I care?

Citizen science is a brand new area of scientific research that has only received proper acknowledgement in the last few decades, and it is an area in which everyone can get involved.

In particular, areas such as bird-watching (ornithology) or astronomy lend themselves to this form of work. This is both because the number of interested non-scientists far outweigh the number of scientists in these fields, and because the scientific method can be simple. The value of such research to generate big data is undeniable!

In a world where even academic research is often directed at only those projects that industry is willing to fund, it is essential that we still support the less economically viable work.

How can I be involved?

What a good question!

There are a massive amount of projects you can get involved in, and many of them are on the website Scistarter in the US, Countryside JobsCitizen Science or even on Wikipedia.

I have been involved with Sea Hero Quest, a game that aids Dementia research through assessing the spatial memory of players. This sort of data is valuable to determine a baseline for what goes wrong in Dementia. This is important because our scientific community is currently struggling to find an effective cure or even a treatment for Dementia and Alzheimer’s disease, and that is partially due to difficulties in early diagnosis.

If you happened to read my post from last week, you may be interested to know that there are also projects involving taking samples from volunteers. uBiome is a company that sequences Microbiome data from paying volunteers. This data could have a massive impact on our understanding of the Microbiome and its connections to human diseases.

Other projects can involve surveys, such as OPAL surveys to assess the state of our environment, bug surveys by Buglife to keep an eye on our insect populations, BirdTrack to give our airbourne friends some help, Treezilla, which is a project to record all of the country’s trees and the list goes on… I’ve just documented some of the nature-related surveys and projects in which I’ve taken part – there are hundreds of projects relating to pretty much any area of science!


A note from the author: As I sometimes write on emotive subjects, comments are disabled after 14 days. This is because ongoing discussions tend to stagnate.


  1. BBC article on Citizen science
  2. The UK Environmental Observation Framework’s details on Citizen Science

Microbiomes and Moods

Our Friendly Gut Bacteria

The recent discovery of the importance of our Microbiome (our “friendly” gut bacteria) has served as a critical reminder to medical researchers that the body does not exist as a series of disconnected notes or phrases, but as a wondrous song with many interconnected melodies and harmonies that each play an essential part. Of course, this is what makes the human body so interesting and wonderful, but it’s incredibly difficult to take into account as a researcher. In fact, a lot of good research comes out of being able to tease out the causal relationship between individual factors and their response.

There are few areas where this is more evident than in mental health research. Various studies have linked depression to inheritance, social factors, general health, drugs, alcohol, hormone levels and the list goes on… But unfortunately a physician cannot counter all these different issues. They require complex intervention that amends all aspects of a person’s life, in many cases.


Using the Microbiome in Medicine

Sometimes this can be all too overwhelming. How can we treat something that is no more under our personal control than government legislation? And this is before we take into account the diagnosis. Mental health practitioners cluster certain behaviours under the umbrella of a certain disease type so as to be able to try certain treatments that have worked for people with those conditions in the past.


The recent research into the Microbiome has suggested that it may serve as a valuable fingerprint, as another way in which we can identify specific areas in which a person’s body deviates from the “healthy norm”. Using this data we could look for critical changes in bacteria levels that may account for nutritional deficiencies or changes in hormone/chemical levels. And this can all be altered by simply altering what we consume.

This gut-fingerprint would simply mean taking a sample of stool from a patient and analysing the different bacteria levels, and then treating their abnormalities with probiotics or even just bacteria. This has been proven to work by several landmark studies into “faecal transplants” wherein unhealthy mice were given healthy stool to successfully fix various disorders.1

What About Mental Health?

So let’s get back to the original premise. Depression in particular is a challenging disorder to treat because patients are idiosyncratic. Unlike in many disorders, it is hard to tell which treatments would be successful. So what if we could find a potential cause of depression by looking at someone’s poop?(1)


That’s just what has been done by several research groups.(2) Many neurotransmitters (used by our brain to talk to itself and other tissues in the body) are produced by bacteria. In particular, serotonin is produced almost exclusively by our Microbiome in adults (80-90% of the body’s serotonin can be found in the intestines). This means that changes in the levels of the serotonin-producing bacteria of an adult can seriously alter the levels of serotonin in their brain. This link is key because serotonin is a key mood regulator in our brain. Specifically, low levels of serotonin or less receptors for serotonin has been implicated in depression, as well as anxiety, panic and anger disorders.

Other work has implicated the Microbiome in GABA-signalling. GABA action is related to calming nerves and treating anxiety. Mice that are stressed during their pregnancy pass on less of a GABA-secreting bacteria to their pups: and these pups thus have lower levels of GABA.

It’s hard to measure depression in mice, as unfortunately they do not respond particularly well to counselling and certainly will not tell you in detail how they have been feeling since you last saw them. But there are certainly some factors we can look at, such as behaviour. Researchers can clearly see if mice are acting less sociable with their peers. They can also do experiments to see if mice give up on impossible tasks earlier, such as in a test where they are unable to escape a tank of water. Those who give up earlier display a higher level of “behavioural despair”.

Mice that are not exposed to the normal levels of serotonin- or GABA-producing bacteria show adverse effects in these behavioural tests, which are reversed upon application of probiotics. Other research undertaken elsewhere has shown the effects of the gut bacteria Bacteroides fragilis in autism, and how mice with “autistic traits” such as repetitive behaviour acted more normally with probiotics. These results have implications in the treatment of autism.

Research has thus shown that the gut Microbiota are affected by stress, development and diet. In turn (in just this look at mental health) the Microbiota can have an affect on our hormone and chemical levels, which has widespread effects on signalling in the brain. This research has massive implications in the types of therapies we could use in these disorders in the future. Much of what is currently used affects receptors in the brain – whereas these therapies could, in theory, target chemical level imbalances at the source.

Our little bacterial friends, in only the short time in which we have been focusing our research on them, have already proven to have massive effects. I’m sure we can look forward to even more advances in the future!

A note from the author: As my posts sometimes touch on emotive subjects, comments are disabled after 4 days. This is because, at this stage, I feel that ongoing discussions tend to stagnate.


Postscript: Going Forward with Mental Health Research

The evidence for trying probiotic treatments for mental disorders in humans looks good! It could be argued that the evidence for this has existed for a long time, and it has. A lot of the chemicals we use in our bodies originate in our gut, and from food we eat. Approximately 50% of patients with Irritable Bowel Syndrome (a condition that requires sufferers to restrict their diet) have anxiety and depression, and this makes sense.

So why have we not considered this before now? Really, interest in research into mapping the human Microbiome only fully began since the Human Microbiome Project plans began in 2007. Why did we not consider before looking into something that weighs about as much as our brain? It’s hard to imagine, but we have only very recently (within the last century) begun to understand a lot about our bodies, particularly the brain. Medical research has come on leaps and bounds since the 19th century, and it is accelerating.

The problem with mental health research is that, in some ways, it has lost its way. In many disorders we have psychopharmaceuticals and psychiatric therapy, and these two unrelated things are combined. The value of both of these two avenues is indisputable, but they are diverging. Alas, the nature of cross-discipline research does not necessarily end itself to cross-discipline therapy. Practitioners trained in one or the other find it difficult to cross over, or may not even want to. It’s the same as asking a heart surgeon to treat an infectious disease, effectively. But it shouldn’t be. Modern medicine is moving ever onwards towards personalised therapy, where every aspect of a patient should be considered in every aspect of their treatment.

In this way, I see this probiotic research as being a bridge that reminds us of what we already know: that considering the patient as a whole rather than a sum of parts is essential to medical practice.

As a special note for this postscript, I would like to point out that I am a chemistry lab researcher with some experience working in clinical science laboratories and with medics. This article is written from my own knowledge, my own experience, and therefore any alternative views are very welcome!




Independent Article

NY Times Article

(1) Michaelides, M., and Hurd, Y. L. (2015) More than a Gut Feeling : the Microbiota Regulates Neurodevelopment and Behavior The realization of the importance of the. Neuropsychopharmacology 40, 241–242.

(2) Kelly, J. R., Clarke, G., Cryan, J. F., and Dinan, T. G. (2016) Brain-gut-microbiota axis : challenges for translation in psychiatry. Ann. Epidemiol. 26, 366–372.

If you’re interested in more information, please have a look at the work of the researchers at University College Cork and McMaster University, there is some fantastic stuff :D.


Ars Medendi reads: Do No Harm

The Book

Do No Harm – Stories of Life, Death and Brain Surgery

Henry Marsh

Weidenfeld & Nicolson, 2014

What it’s about: A Summary

I don’t want to spoil the book by giving too much away in this summary. I would simply say that, if you are looking into a career in the medical profession, this book is an excellent resource.

Simply, Do No Harm is the memoirs of a senior neurosurgeon, from the beginning to near the end of his career. It encompasses the good, the bad and the ugly of his field and medicine as a whole.

I would not say that Henry Marsh is a good role model for budding doctors. I would instead say that he acts as a reminder to all that doctors are as human as the rest of us.

On the Author:

Henry Marsh is one of the UK’s foremost neurosurgeons. It should be noted that, although I felt that only a cursory amount of attention is paid to his work in Ukraine in the book, the film The English Surgeon details this in far more detail. If you find this book to your tastes, it is worth giving the film a watch.


The Review:

“It is not surprising that we invest doctors with superhuman qualities as a way of overcoming our fears. If the operation succeeds the surgeon is a hero, but if it fails he is a villain.”

Henry Marsh is only human. In his memoirs he publishes truly honest, sometimes disturbingly honest, stories of his daily life and work. In it, he challenges the basis of the age-old Hippocratic oath “Do No Harm”, by reminding us that, in their humanity, doctors and even surgeons make mistakes more often than we care to admit. Even truly excellent ones! In fact, all fields of medicine and all treatments come with risks that cannot always be accounted for. Walking along the corridors of a nursing home, he recognises “at least five” of the residents as his own failures. And these failures are what populate the book from page 1. “The idea that neurosurgery is some kind of calm and rational appliance of science… is utter crap.”

In fact, Marsh provides a window into his world in a very honest sense. Neurosurgeons must, on a daily basis, make life-changing, or life-saving, decisions that could lead to immense success or utter failure. It is with this dilemma that Marsh presents us.

In the course of the book, we also can see the sacrifices made in the pursuit of becoming an excellent neurosurgeon. The career served to shape Marsh’s character, such that he feels a certain entitlement as a result of his importance at work. One particularly memorable example of this is the moment in the book where, after performing a protracted operation, he expresses frustration at the menial world outside the hospital by imagining asking the person in front of him in a supermarket queue “What did you do today?” It is this frank self-awareness of how pompous he sounds that makes Marsh somehow so relatable.

Marsh, conversely, approaches the subject of being treated as a patient by his colleagues, and seeing his close family treated as well. It is through this intense vulnerability that he understands the plight of his patients. Through the connection Marsh makes to his patients, we can see the powerful exhilaration in performing a successful procedure to save a life. It is the wonder that Marsh feels that we also feel, even starting as a trainee first working on the brain, “a mystery… as great as the stars at night and the universe around us.”

And yet, the book still feels like a cautionary tale of the old ways of medicine: strict hierarchies where the senior doctor’s word was law. The world Marsh trained in, whose values are so ingrained in his practice, is gradually fading away, turning him into an “impotent and angry victim of government targets”. And it is being replaced with fresh bureaucracy, new management structures, corporate training programmes and regulation of junior doctors’ working hours. We can all certainly relate to the bizarre frustration he feels at current juniors being free of the excessively-long hours he endured as a trainee, but he also describes with understandable anguish administrative staff brought in purely to police government policies and agency staff that do not know the whereabouts of their patients.

It is with these thoughts that the book ends. It is an appropriate finish to a book that encompasses the daily thoughts, successes and failures of a human being who is also a surgeon. And really that, in itself is poignant in this new era of personalised medicine: in the same way that doctors must view patients as human beings, we must acknowledge that doctors, too, are people with their own hopes, desires and full lives.


A note from the author: As my posts sometimes touch on emotive subjects, comments are disabled after 14 days. This is because, at this stage, I feel that ongoing discussions tend to stagnate.

Ars Medendi reads: The Man Who Mistook His Wife for a Hat

The Book

The Man Who Mistook His Wife for a Hat

Oliver Sacks

Picador, 1986

What it’s about: A Summary

Welcome to the world of a neurologist. Oliver Sacks compiles many case studies he has published in medical case journals. These serve both as incredibly insightful looks at particular neurological disorders.

This is the only one of Sacks’ books I have read, but it is the most iconic. And it is worth a read for anyone interested in the subject area. In fact, I would recommend it as a window into the personal nature medicine takes on especially in matters of the brain, our most misunderstood organ.

The Review:

“Constantly my patients drive me to question, and constantly my questions drive me to patients – thus in the stories or studies which follow there is a continual movement from one to the other.”

Throughout the book, Sacks refers to Luria’s neurological case work, and he uses his extensive knowledge to craft the cases, peppering them with appropriate quotations and scientific context. And yet throughout, the patients are depicted as profoundly human and deeply sympathetic. It is these patients that lie at the centre of the book, and at the centre of Sacks’ life.

Oliver Sacks’ book is varied by the different tales in it. Therefore it stands to reason that a review should look into each section separately.


This section of the book encompasses the deficits, or the “A”s – Aphasia, Ataxia, Agnosia etc. It is this section which includes the iconic “The Man Who Mistook His Wife for a Hat” – the true story of a man unable to visually process shapes and assign them with identify. It is for this reason that, during his interview with Sacks, he “took hold of his wife’s head and tried to put it on”. This section of the book explores the impact of memory disorders. Another story “The Lost Mariner” describes a man trapped in his past, unable to form new memories or understand his present.


This section is perhaps the opposite to Losses, comprising of manias and hyper-activities of the brain such as Tourette’s. Striking is the story of one man plagued with the latter (“Witty, Ticcy Ray”), wherein the patient decides that he will only undergo treatment by Haldol for his condition on certain days of the week. It is in this way that we can understand how intrinsic the workings of the brain are to a person’s personality and creative ability; such that, perhaps, we cannot treat the former without affecting the latter to a degree.


This section is exactly as it sounds. Stories of patients transported elsewhere by their brains. “A Passage to India” is a story of an Indian girl with a malignant tumour that expanded to compress areas of her brain. It is at once a melancholic and beautiful tale. In a way, her visions of India were her salvation from an impossible prognosis, as understood fully only by her: “I like these dreams – they take me back home.”

The World of the Simple

It is this section that explores the world of the “autistic savant”: those dismissed due to their placement on the autistic spectrum, but who have intense creative or mathematical talents. “A Walking Grove” is the story of a man with severe developmental deficiencies able to ”retain an opera or an oratorio on a single hearing”. Is it through these abilities that he develops with relationship with his musical father, despite being unable to express himself through other means.

Bottom line: if any of these cases sounds interesting to you, I highly recommend picking up this book. It is truly extraordinary.


A note from the author: As my posts sometimes touch on emotive subjects, comments are disabled after 14 days. This is because, at this stage, I feel that ongoing discussions tend to stagnate.