BBC Documentary - Pain, Pus and Poison - Part 2

Following Part 1 of this BBC trilogy of medical documentaries, presenter Michael Mosely focuses on our ability as humans in tackling some of the most serious, and fatal bacterial, fungal, and viral infections. One of the biggest feats of human medical intervention ever has been the eradiction of the smallpox virus, the culprit responsible for millions of deaths in that dark period of the epidemic. Featuring this, and other major infectious diseases, Dr Mosley narrates a scientific journey through which numerous scientists, doctors and corporations worked together to find the elusive cure.


It starts with an account, describing the last moments of the life of George Washington, the first president of the United States. Mosley comments that he probably died from a simple infection - the fate of million of people around the globe at that time, a time which medicine as we know it was very primitive. Even the 'best physicians' in the country could not find a successful solution for President Washington. This is an alarming contrast to today's world, where a small scratch proves nothing significant at all, but back then, it could lead to something life-threatning. Even in World War 1, more soldiers died of wound infections, than from 'direct hit'.

To appreciate just how dangerous bacterial and viral infectious agents are, and how easily they can spread, Dr Mosley visits the Centres for Disease and Prevention (CDC) in Atlanta. It is one of two centres in the world that currently contain repositories of the deadly smallpox virus, with virtually unbreathable security. Even the BBC had extremely limited access. If the virus were to get into the wrong hands, the consequences could be disastrous - many precautionary measures are in place to minimise this possibility indefinitely. The CDC holds some of the worlds 'worst serial killers' to put it simply.

In the 1790's America especially, microbes weren't remotely considered to be the cause of such sudden deaths such as Washington's. Only after the Germ Theory was discovered, that people's perceptions began to change regarding infection and disease. Through subsequent wars in history, medicines advancements have been accelerated - medical science has professed to a point where we may be considered 'ahead of our time'.

Even further progress came when Methylene blue dye was dissevered by Paul Ehrlich to be remarkably effective in 'illuminating' the hidden world of bacteria. Staining is still used enormously today, so that we may appreciate how complex the small world really is. With the right stain for a particular bacteria, scientists were able to make discoveries into how a certain bacteria strain causes a particular disease.

From here, the next step was to find substances that can destroy these bacteria - we have been seeking 'magic bullets' ever since.

English Surgeons to Publish Death Rates in New Proposals

In the news this week there's been some controversy over the proposals set by NHS England regarding the publishing of data on surgeons. More notably, the publishing of death rates by surgeon. Sir Bruce Keogh, Medical Director of NHS England has said "surgeons must publish the death rates for their patients or face penalties". This raises concerns over whether current surgeons will continue to practice under further statistical scrutiny. Indeed this has been a 'move to increase transparency', perhaps in a way too drastic in the view of many surgeons across the country. With over a decade of medical training, we should trust surgeons to have the best of intentions for every patient, no matter the condition, no matter the person. Perhaps this new movement will question every single surgeon in the country of their competency, and the techniques they utilise in the operations they carry out.

Sir Keogh also added that "we will lose some surgeons...as a consequence of this endeavour". In addition, he made the point that as those surgeons doing few operations may avoid attempting more under this new regulation, more procedures will be 'passed' between colleagues. The potential advantage is that surgeons will have their work load slightly reduced, enforcing the importance of quality, not quantity when performing surgeries. A heart surgeon himself, even though he is involved heavily in this field, he is adamant that 'this is not going to go away'.

Above: Surgeons performing operation (Wikipedia)

Let us consider the implications of this. The statistics shown for death rates may be physically true, but in the wrong context, they may be misleading. If so, this would provide doctors and governing bodies to make invalid conclusions. It will be important for surgeons to publish all deaths to make the results valid. For example, one particular heart surgeon may have a 'significantly high death rate', however it may be overlooked that he is considered the best in his department, having most extremely difficult operations passed onto him by his colleagues. Currently, most surgeons do publish death rates, and the patient has control on whether they would want an operation from a particular surgeon 'based on their figures'. I believe that there is a danger that patient could make poor decisions from these statistics alone, for reasons above, and that they may overlook the expertise and experience of a surgeon. Therefore it is important other factors are considered and presented to the patient for them to make a fully informed decision.


Credit to Ben Tufft for his article 'NHS Medical Director: Surgeons must publish death rates', published in The Independent, 16th November 2014. The full article can be seen here

Are You Getting the Right Match?

In the UK, there has been a big increase in the number of patients requiring transplants over the last decade or so. In fact, this pattern can be reflected worldwide. In order to understand why we need more donors to accommodate the continual increase in patients requiring transplantation of solid organs, its useful to know how we determine matches between donors and patients. "Solid" organs as you could infer, relate to organs that are in a solid state. Examples of these include the kidneys, pancreas, heart and lungs. It is widely accepted that it isn't easy to find compatibility between donor and recipient straight away - there must be biological compatibility of two types. The first is the well-known ABO blood group system. There are four different groups that an individual can fall into: A, B, AB, and O. Each group signifies the types of antigen present on the surface an erythrocyte, or red blood cell. Antigens are proteins on the plasma membrane of a cell, giving it its own 'identity'. This is essential in the multiple processes of the immune response, for example. A person identified with an 'A' type blood group has only 'A' type antigens on the cell surface membranes of red blood cells. However they will also have 'Anti-B' antibodies circulating in their blood plasma. The converse is true for those with a 'B' blood group. If someone were to have AB however, they would have both types of antigen on the cell surface membranes of red blood cells. Therefore no antibodies acting against these antigens would be circulating in their blood plasma. Now, those with type 'O' blood group are seen to be rarer than those with other blood groups, but it means as a donor you would be 'compatible' with any recipient of any blood type. For this blood type, no ABO antigens are present on the membranes of red blood cells, but the serum of these individuals will contain the 'Anti-A' and 'Anti-B' antibodies.

Chart showing the differences in cell type, antibodies and antigens present in individuals with different blood groups (Source: Wikipedia )

To illustrate this, let us consider a potential liver transplant between a donor with blood group O and recipient with blood group B. The donor has red blood cells with no ABO antigens, so when mixed with blood (and plasma) containing red blood cells with the B antigen and therefore 'Anti-A' antibodies, there will be no immune response. After all, the antibodies are not able to form an antigen-antibody complex.

Most people will be aware of the ABO blood group system; however there is another factor that always needs to be considered by doctors before carrying out any surgeries involving organ transplantation. This is what is known as the human leucocyte antigen (HLA) system. All cells known to contain nuclei in the body possess these protein complexes on their cell surface membranes. Therefore it is useful to know that red blood cells do not have these antigens as they have no nuclei, no genetic material encased. HLA types are inherited from both parents, and 'research has shown that the fewer the number of mismatches between donor and recipient HLA, the less likely it is that the organ will be rejected post-transplantation'. This is why it has become increasingly imperative for doctors to screen individuals for this type of antigen so that matches between patients and potential donors can be confirmed. A patients HLA type can be confirmed by a series of tests. The polymerase chain reaction (to create multiple copies of DNA) followed by gel electrophoresis (allows the scientist to visualise the result) being one of the more notable methods.

After the HLA type has been confirmed, the patient's serum is analysed to 'screen for the antibody profile'. Firstly, the serum is 'mixed with microbeads that have multiple HLAs on their surface'. This essentially serves to identify antibodies that are targeted at particular donor HLAs, using a fluorescent marker. This is needed as there is always a possibility that the recipient could have developed antibodies against a particular HLA in the past, whether it be pregnancy, previous transplants, or blood transfusions. These are known as 'sensitisation events'.

In addition to this, another test is carried out, involving mixing of recipient serum with donor cells. This is primarily to see if there is any immunological reaction to the donor cells, thus proving whether a donor is in fact compatible with the patient. The donor cells are those with nuclei, so scientists can test whether the HLAs of the donor form an antigen-antibody complex with antigens present in the patient's serum. 'Complement' molecules are also added which help to destroy cells (by lysis) that have their HLA antigens bound to patient antibodies. To see whether a reaction has occurred or not, a visualisation stain is applied, dead cells staining red, and live cells staining green.

Not only is it important to choose the right donor, but selecting viable organs for surgical use is also vital. Donors can either be living or deceased, but living donors 'are generally family members or close friends of the patient'. That isn't to say all are, of course, as altruistic donors are on the rise - these people are willing to donate an organ without knowing who will receive it in due course. Kidney donation is by far the most common transplantation from live donors. In fact, 'in the UK, 2732 out of 3740 transplants performed in 2011 were kidney transplants'. Donations from the deceased however can be divided into two sub-groups: those who are pronounced brain dead (DBD), or those with circulatory death (DCD). DCD is when the heart has completely stopped beating and thus there is no circulation flow throughout the body. DBD donors have organs 'kept alive' by a ventilator, with a constant blood supply in place.

A patient can be found to have their donated organs rejected by their own immune system at several possible stages after surgery:

Hyperacute: Rejection occurs immediately, even within a few minutes of transplantation. Surgeons would need to work quickly to remove the donor organ completely from the body. Nowadays, hyperacute rejection is very rare.

Accelerated acute: Rejection could happen within a few days to a week after surgery. The rejection may be due to the fact the patient has experienced a sensitisation event in the past, which produced the relevant antibodies.

Acute: Rejection occurs within the first 6 months of surgery, and is mainly due to a few mismatches in HLAs between the donor and the patient. This sort of rejection can be brought under control with certain immunosuppresant drugs that are specific to the recipient.

Chronic: Rejection could even occur after 6 months from the point of surgery and mainly due to repeated episodes of acute rejection. This is the main problem facing patients with transplants - some patients will be required to take immunosuppresive drugs for the vast duration of their life.


With a population as ethnically diverse as the UK, it has become increasingly difficult for those of minor ethnic origins to receive the right matches for organ donation, although overall there is a big gap between the numbers requiring transplants and willing donors.Those of Black and Asian origin have been known to have 'uncommon HLA types'. Many countries, such as Spain, Belgium, France and the USA have implemented an 'opt-out' scheme nationwide. This means it is presumed you give consent for your organs to be donated, unless you state otherwise. In the UK, the public's view may be changing on whether we should carry on with our current system in order to meet the piling demand for organs across all ages, all backgrounds, and all ethnicities.


Credit to Steven Jervis, clinical scientist at the Manchester Transplantation Laboratory who wrote for the Biological Sciences Review (Volume 24, Number 1)

"Dead Heart" Transplant - World First in Cardiac Surgery

In Australia this month, surgeons have managed to resuscitate a heart from circulatory death and use it for transplant in patients with 'end-stage heart failure'. Prior to this, hearts used for transplant were only sourced from brain-dead patients but whose hearts were still beating. Some have heralded this as a 'paradigm shift' in organ transplantation. The heart was able to be revived using what has been  dubbed as the 'heart-in-a-box' machine (the OCS - Organ Care System). Now the machine is commercially available to hospitals in Europe and Australia for clinical use. Usually, a beating heart is kept iced for a long period of time, however this machine is claimed to be a 'portable, warm perfusion, monitoring machine'. As of now, St. Vincent's Hospital Heart Lung Transplant Unit in Australia has transplanted two patients using this technique. However it is important to note that the OCS has already been used and approved for other types of transplantation such as the liver, kidneys and lungs. Up until now, it has proved difficult to repeat the same technique on 'dead' hearts.

The benefits of this new technique prove essential - the maximum possible number of donor hearts available will inevitably increase. In fact, it is estimated that 30% more lives could be saved with the introduction of this technique. Professor Peter MacDonald, Medical Director of the St Vincent's Heart Transplant Unit has said "this is a timely breakthrough. In all our years, our biggest hinderance has been the limited availability of donor organs". With regards to the OCS machine, portability is useful if it is needed in various departments in a hospital. It would also mean ease of transportation nationwide, or even worldwide.

 

Top: OCS "Heart-in-a-box" machine (TransMedics)

Above: OCS machine maintaining liver for transplant (BBC)

Interestingly however, this isn't the first time that this idea of using a dead heart donor has been experimented. Professor Kumud Dhital perfumed both of the operations in Austrailia says that "It is interesting to note that DCD hearts were utilised for the first wave of human heart transplants in the 1960's with the donor and recipient in adjacent operating theatres. This co-location of donor and recipient is extremely rare in the current era leading us to rely solely on brain dead donors -- until now".

The recovery of patients is even more astounding. Michelle Gribilas, 57, was the first patient to be treated with the surgery. Before the operation she was suffering from congenital [end-stage] heart failure. Two months after the procedure, she told the BBC: "Now I'm a different person altogether. I feel like I'm 40 years old - I'm very lucky". Senior cardiac nurse at the British Heart Foundation, Maureen Talbot, added "without this development, [patients] may still be waiting for a donor heart".


Credit to the BBC for their article 'Surgeons transplant heart that had stopped beating', published 24th October 2014. More on the subject can be found here.

Credit to St Vincent's Health Australia, whose story was published in ScienceDaily on October 24th 2014. The original article can be found here.

BBC Documentary: Pain, Pus and Poison - Part 1

Over the last 150 years or so, the story of the advancements of drugs, treatment, and techniques in medicine has developed at a great pace. Dr Michael Mosley recently presented a trilogy of documentaries for the BBC, telling tales of the beginnings of anaesthesia and the birth of the antibiotic era. In part one of the series, he focused on man's pursuit to free pain. It begins where you may not expect - the poppy. From this rather innocent-looking plant, a resin was extracted and given the name opium. Dissolved in alcohol, the medicine was called laudanum. Morphine, the drug we are familiar today with unprecedented properties in alleviating excruciating pain, was formerly discovered by 19th century pharmacist Friedrich Sertürner. Morphine works by blocking nerve endings associated with pain at the site of pain and in the brain. The direct blockage of these signals proves morphine very effective. Eventually isolating the active ingredients in raw opium, he had managed to obtain a substance that could now be quantified and measured for ease of administration. This fact is often underestimated about drugs - simply by being able to measure out a quantity of a substance offers a huge element of control and indeed safety. It was considered back then that medicines which originated from plant sources were alkaloids, containing the suffix -ine in their name. Hence we are familiar with morphine, whose former name was morphium. According to Dr Moseley, these alkaloids were considered 'our first real medicines'. Dr Walter Sneader, Former Head of Pharmacy at the University of Strathcylde says that the discovery of morphine was 'the single most important event that has ever occurred in drug discovery - far more important than the introduction of penicillin, in terms of advancing the science'. Sertürner then went on to isolate many more alkaloid chemicals, some of which include caffeine, nicotine and quinine. Another well known alkaloid that was discovered was cocaine. Ironically enough, at the point of introduction in industry this compound dissolved in alcohol was approved by the Pope himself. The famous neurologist Sigmund Freud went on to investigate more into the properties of cocaine.



Although these alkaloids were a start, these weren't considered potent enough to be effective in the operating theatre. Sir Humphrey Davy saw nitrous oxide as a potential drug for use in surgery, however surgeons still went on to attempt operations on people who were unfortunately, fully awake. It was only until William Morton and the introduction of ether as a gaseous anaesthetic agent, that anaesthesia started to advance rapidly. To read more on the subject of William Morton's discovery, visit my post, 'The History of Anaesthesia'.

After this remarkable discovery, chemists from all around the world began to experiment with various substances, coal tar notably being one of the 'more unlikely places'. Chemist and presenter Andrea Sella, mentions that using coal tar was able to open 'a whole new library of starting materials'. Some of the most iconic drugs in today's world were a product of this seemingly unpromising raw material, aspirin and heroin just to name a couple. In the 20th century, many more drugs with anaesthetic properties were developed. However it wasn't just anaesthetics; the world's first sleeping pill was discovered, chloral hydrate which became very popular. The barbiturates were another group of drugs that had the ability to put people to sleep. Sodium thiopental was one of the more notable ones, the 'truth drug' so given the name for it's use in interrogation, is featured in the documentary.

Now in the 21st century, we have made great strides in the development of even more effective and safer drugs for use in surgery, prescription, and treatment of diseases. It has come to a point where we can, with suitable starting materials such as simple molecules, develop any molecule we want to. This means we can develop any drug we want to. A surge in technological advances in the last few decades has supplemented our understanding of anaesthesia and how pain is managed.


Credit to the BBC for their medical documentary trilogy, 'Pain, Pus and Poison', broadcasted in September 2014.

Repairing Damaged Heart Tissue With Embryonic Stem Cells

Heart disease is now considered the most common cause of death in the UK, according to the BBC. This pressing issue has initiated research projects to find the best treatments, long-lasting treatments that involve the regeneration of heart tissue. Experiments back in 2005 involved deliberately inducing heart attacks in 18 sheep in order to test the potential of embryonic stem cells from mice. Research prior to this revealed that attempting to use stem cells from the patient would prove futile as adult stem cells do not have the capacity to differentiate into heart (cardiac) tissue. If this was possible, this would undoubtedly be a desirable solution as the patient's own cells are being used, reducing the risk of rejection.

Therefore embryonic stem cells have been labelled the next hope in the regeneration of damaged heart tissue. The experiment back in 2005 involved separating the sheep into two groups, one the control, the other being given 'multiple injections' of the embryonic stem cells [from mice] after a rest period of two weeks. These cells had been given growth factors to trigger them into developing into cardiac cells. Five sheep from this group were also given immunosuppressants in case there is an issue of rejection. Tagging the stem cells with 'fluorescent proteins' helped scientists to track their progress of colonisation, which was successful after one month. As anticipated, the cells were effective in regenerating the heart tissue in the non-control group, replacing the scarred tissue. In fact, the scientists were able to measure the heart's effectiveness to pump blood from the left ventricle. In the control group, blood ejection rate decreased by an average of 6.6%, whilst it was raised by 10% in the group given stem cell treatment.

By this data, the treatment seems very effective, however only 18 sheep were used in this set of experiments and embryonic stem cells of mice were used. Nevertheless the fact that this technique works in principle gives hope of new treatments involving stem cells. What was more encouraging for the scientists, is that there was no evidence of an attempt of rejection by the immune systems of sheep that were administered immunosuppressant drugs. However geneticist Robin Lovell-Badge, researcher at the National Institute for Medical Research, London, says that there is a "need to be cautious. Other tissues might reject the stem cells". He also pointed out that the sheep were only monitored for one month after the investigation. Side effects to the treatment or rejection could well occur further down the line - this is another implication for human trials.

Since these experiments, another study at the University of Washington Institute for Stem Cell and Regenerative Medicine also found success in the use of embryonic stem cells to regenerate tissue, this time in monkeys. The study summary stated that the stem cells "assembled muscle fibres and began to beat in synchrony with macaque (monkey) heart cells". What was interesting is that this time, human embryonic stem cells were used. The findings were published 30th April 2014 in Nature. 

Above: Green areas depict newly transplanted stem cells forming a graft with the primates original cardiac muscle cells (red). Full credit to the University of Washington

Credit is given to Anna Gosline, writer for New Scientist. Article can be found here. Original study findings can be found in The Lancet (Volume 336, pg 1005). 

University of Washington findings report can be found at ScieneDaily here.

World First In Organ Transplantation

Recently in September, it has been revealed that a woman in Sweden gave birth to a baby boy, only possible with a womb transplantation. This pivotal event in medical science has given hope to thousands of women around the globe who are unable to conceive. Some cancer treatments and birth defects are a couple pf the reasons why women have this problem. The donor of the uterus was a friend of the 36-year old, who was in her 60's at the time of transplantation. The birth was successful, however premature at 36 weeks, the baby weighing in at 1.8kg (3.9lb). Prior to the birth, the unidentified couple underwent IVF treatment in order to produce 11 embryos. These were frozen until the point of transplantation at the University of Gothenburg. As with the vast majority of organ transplants of today, the woman was given immunosuppressant drugs before the transplant, in order to reduce the risk of rejection by her own immune system.

After the transplant, doctors were then able to select an embryo from the ones frozen to implant into the new uterus. However this was only after a period of a year. In the short period before the birth, the baby was said to have developed an abnormal heart beat, hence the premature birth, however now the baby's condition is said to be 'normal'. However complications with this sort of transplant don't just stop there. If the couple were to have a second child, they would need to consider the fact that the immunosuppressant drugs can be 'damaging in the long term'. It would be considered that if they decide not to have a second child, then removing the transplanted womb would be a necessary precaution.

There have been several fails attempts at womb transplants, whether it be due to the organ becoming diseased, or birth resulting in miscarriages. Now, Professor Mats Brannstrom, who led the surgical team expressed relief and happiness in response to the success. In fact it has emerged that two more women will be receiving womb tranplants by the end of this year; suregons in the UK will be choosing 5 patients out of 60 who will undergo this potenially life changing opeation, according to the Sunday Times.

"Our success is based on more than 10 years of intensive animal research and surgical training". Despite the success however there are still concerns about the 'safety and effectiveness of the invasive procure', according to the BBC. This breakthrough is somewhat comparable to the leap in medical science that IVF allowed over 30 years ago. The Chairman of the British Fertility Society, Dr Allan Pacey said the operation "feels like a step change", however he is aware that it will need to be proved repeatable, reliable, and safe in the future for many more patients.


Credit to Oliver Moody, for his article 'More womb transplant babies on the way' which can be found here.
Additional credit to James Gallagher, Health Correspondent for the BBC, for his article 'First womb transplant baby born', which can be accessed here

Obesity And Its Expensive Relationship WIth The NHS...

Recently, the NHS chief executive Simon Stevens issued a statement to the public at the Public Health England conference in Coventry, which is held each year. In the light of an on-going obesity epidemic, he believes that "Obesity is the new smoking". Describing the disease as a "slow-motion car crash", he, along with thousands across the country, recognise that the costs involved in treating obesity has risen year on year to a point where it'll become unsustainable without raises taxes.

Basic statistics reveal how vast the problem is: 25% of adults and over 20% of children are considered obese. I encourage you to see my other article, 'Fat!', for more interesting statistics.

By many, obesity is considered a disease of all age groups, which makes the numbers affected much larger. Tackling the issue therefore proves an expensive task, as currently the government spends around £9bn every year on treatments.

Stevens added that Britain would be 'piling on the pounds in terms of future taxes'.

Percentage of men and women obese from 1993 - 2009 (BBC article)

However its important to appreciate that obesity isn't just an isolated disease. In the majority of cases, obesity will inevitably lead onto other complications including cancer, diabetes and heart disease. Treating people for these additional problems will only increase the overall cost of treatment. At present, the most common direct treatment for obesity (especially those morbidly or severely obese) is bariatric surgery. There are two main types - gastric band and gastric bypass. A gastric band uses a restriction of stomach size, so than when food is ingested, less is required to make you feel 'full'. The alternative method is a gastric bypass, 'where your digestive system is re-routed past most of your stomach'. This gives the effect of digesting less food, having a similar psychological effect to a gastric band. Despite the obvious benefits, patients are always made aware of the potential complications to their health post-surgery. Internal bleeding or deep vein thrombosis (DVT) are just a named couple. Generally however, patients are enrolled onto a 'rigourous and lifelong plan', including regular exercise and a monitored diet, according to NHS Choices.

However this measure may only be considered suitable for those whose life is at risk and require emergency intervention. Those who register as 'overweight' on the BMI scale, are currently not legible for bariatric surgery.

But how can the nationwide problem be tackled? According to the BBC, one of the future proposals would be to increase spending on 'lifestyle intervention programmes' rather than bariatric and similar surgery. This will be a step forward in combating obesity in the long term. Surgery could be considered a relatively short-term solution. 

Credit to Nick Triggle, BBC Health correspondent, for his article published which can be read here. Also the full speech by CEO Simon Stevens can be read here.

The Small Guys That Help Regulate Protein Synthesis

If you have an interest in cellular biology, the chances are you've come across the different types of nucleic acids that are used to code for proteins and control certain activities of the cell. However, what might be new to you is the existence of MicroRNA or miRNA, in its common notation. Essentially these are regular strands of RNA but very small - in fact a regular sized RNA molecule may be around 100 times longer than the average length miRNA. As miRNA are single stranded, the molecules tend to quite flexible, in contrast to the well known rigid DNA double helix molecule. Originally, scientists tended to believe that in eukaryotic cells at least, there were only two types of RNA: ribosomal RNA and messenger RNA. At first, miRNA were seen to be RNA that were too insignificant to have any real function, they were considered free clumps of nucleotides in short.

Now the importance of miRNA molecules has been realised, thanks to cutting edge research on a particular type of nematode worm - specifically Caenorhabditis elegans. In 1993, the first miRNA identified was named lin-4. What scientists found is that somehow, these minute molecules prevent the development of the larvae. 

After these baby steps into this field of research, the year 2000 saw the discovery of the miRNA molecule let-7. This was found to 'regulate development in C.elegans'. What was more significant however, was that this molecule could be found in all animal and plant cells. But what do we mean by 'regulate development'? This particular miRNA molecule is found to be responsible for controlling aspects of the cell cycle and cell differentiation. But healthy functioning cells doesn't rely on a single miRNA molecule - many different molecules working together ensure cellular processes go on as intended.

But how do miRNA's work?

In an average human cell, over 1000 different miRNA molecules can be found. Each of these specific strands seek to target a particular RNA molecule. With over 60% of RNA molecules being targeted by miRNAs, it could be said that controlling protein synthesis is a very organised and vast operation. What is important to note, is that miRNA molecules are encoded by genes, a lot like proteins in fact. It follows that these genes are present in the cell's DNA.

To synthesise miRNA, firstly one long strand of specially structured RNA is manufactured from miRNA genes. These could be considered the precursors of miRNA (Pri-miRNA) and are subsequently lysed by enzymes and transported from the nucleus, into the cytoplasm. Any two different  miRNAs can align through regular RNA-RNA hydrogen bonded base-pairing. However in some parts, there may be some non-complementary base pairing which would lead to bulges from the molecule. Using specific enzymes, the hydrogen bonds can be broken to leave two separate miRNA molecules which can go on to target their designated RNA molecule.

Due to inconsistencies in base pairing with an mRNA molecule, miRNAs have been found to inhibit protein synthesis by preventing the ribosome translating the RNA molecule. But another way miRNA's function is that they can achieve complete complementary base pairing with an mRNA molecule. Specific degrading enzymes can then recognise this situation and destroy the miRNA-mRNA complex, preventing the protein ever being synthesised.

(Two examples of pri-miRNA - sequences in red represent 'mature' miRNA. Notice there are bulges where there is no complementary base pairing - WIkipedia - microRNA)

Extended research has shown that 'malfunction of miRNAs is implicated in some liver diseases, diseases of the nervous system, cardiovascular disease, cancer and obesity'. One example given in the September issue of the Biological Sciences Review is miRNAs affecting normal nervous function. Individuals with mental retardation sometimes have whats called "fragile X syndrome", where as implied, the X chromosome tends to break easily. In association with this, it has been found that in the nerve cells of these individuals, miRNA molecules have prevented the synthesis of an essential protein by binding with mRNA.

Even miRNA has been believed to be the culprit in some cancers. It isn't always bad that an miRNA molecule binds to RNA - some miRNAs suppress tumour growth whilst others promote it.

At present, it may be difficult to see how miRNAs can be used to treat disease, but I believe there is no doubt that it could one day be widely use to diagnose them. Cancers are a good example. It has been observed that particular concentrations of a miRNA can correlate with different rates of growth of malignant tumours. From miRNA analysis, it may be possible for doctors to predict the best treatment options for patients.

However this does't mean treatment isn't possible! According to Professor Sheila Graham of the University of Glasgow, new research has revealed the potential of "miRNA sponges" in cells. These are non-functioning RNA molecules that "mop up" specific miRNA molecules so that they can't interrupt the synthesis of essential proteins.



Credit to Professor Sheila Graham for her article 'MicroRNAs - small players in big diseases' published in the Biological Sciences Review (Volume 27, Number 1).

Documentary on Tissue Donation

Recently I watched a documentary on the BBC about tissue and organ donation - it focuses on the various people that work in tissue transplantation and those who obtain skin and bone from the deceased. It was really fascinating to see how healthcare workers manage the deceased and what happens to tissue when it is obtained and used to treat patients who long for a donor. It has also made me appreciate that the field of medicine is more than 'dealing with the living'. The documentary was called "The Human Tissue Squad" and I encourage anyone to watch this, although those who are squeamish about blood I advise not to!

Here is the video embedded below:



What is especially striking is that this whole sector of healthcare is solely dependant on people opting for their loved ones' tissues to be donated, and people themselves registering onto the organ donation register. The documentary follows staff at the National Tissue Bank in Liverpool during a time of struggle to obtain tissue surgery on patients who have very particular conditions. One member of staff in the film stressed that "it's younger donors that [they] really need". In the last year this documentary was filmed, only 51 donors were under 35.

The National Tissue Bank stores an incomprehensibly diverse range of tissues, from eyes, to femoral arteries, to Achilles tendons. Tissues generally need to be collected as early as 24 hours after death. However sometimes there is a rising pressure from the bank to supply tissues needed by surgeons in many different hospitals around the country. I was also amazed at the work the nurses do at the bank to support the loved ones of those that have very recently passed away. They talk with families over the phone to decide whether tissues will be donated from the deceased. I can empathise that this could be a distressing task, one nurse mentions she takes up to 24 calls a day. Despite recognises these sad losses, it is of importance that they have enough tissues in stock in supply to the many nationwide hospitals. In one week, the bank may go without one single donation, the next, it may be a 'mad rush' to distribute the tissues with as many as four teams a day on the shift.

One outstanding factor that renders the National Tissue Bank being effective is the teamwork between colleagues within small groups. Also, there is a defining commitment to the job as one pair have to venture out for dissection as early as 5:00AM.

The importance of tissue donation means lives can be saved, however there is always a need for tissue supplies. This relies on the difficult decisions of thousands of families all over the country. An interesting question to consider is whether by law, everyone should be enrolled onto the organ doner register - then it is up to the individual to un-enroll.


Credit to the BBC for their televised documentary "The Human Tissue Squad" (available on iPlayer until 15th September 2014)

Fat!

One of the major health issues facing our world, the western world especially, is obesity. In fact, it is estimated that there are over 1.4 billion people overweight with over 500 million obese. These figures are expect to rise. In 1971, it was estimated that in North America, 14.5% of the population were obese. Now, the figure is over double at 30.9%. These figures were taken from the Biological Sciences Review article 'Lifestyle and Cardiovascular Disease', Volume 26, Number 2. Britain, despite it's small land mass, is considered the second 'fattest' country in the world - in reference to it's people that is. It is not only to do with the fact our country is now becoming overcrowded, our very habits, morals, behaviour and eating patterns have contributed to a dramatic increase in cases of obesity in the last couple of decades. To many people, carbohydrates contribute to the base of a diet. However in many cases an imbalance of this food group inevitably leads to weight gain and the formation of excess fat (adipose) tissue. How does this mechanism work? Well, central to this question is respiration, adipocytes (fat cells) and of course the different types of fat. Here, I want to explain how a weight gain is achieved, even right down to the molecular level.

Firstly, we need to understand that the molecule glucose makes up the vast majority of carbohydrate-based foods. Glucose is essential to our well being, in particular being vital to the function of our nervous system and our muscular system. It's uptake by our many billions of cells initiate the start of the production of the 'energy' molecule ATP, or Adenosine Triphosphate. It is a continuous process, however once our cells are content with the amount of glucose needed to produce ATP, glucose is transported and stored in various tissues of the body.

Adipocytes

Usually, glucose can be converted into glycogen via glycogenesis for "short-term" storage in muscles and the liver. Glycogen can be easily hydrolysed back into glucose for ease of access to body cells and tissues. However alternatively, glucose can be stored as part of fat molecules called triglycerides. These molecules comprise of a glycerol backbone with three attached hydrocarbon chains. These chains were originally carboxylic acids, better known as fatty acids - they take part in a condensation reaction to release three water molecules in forming a triglyceride. The main site in the body in which we would find triglycerides is in adipocytes. However triglycerides can also be utilised by muscle cells in the release of energy if needed. Fats are generally considered a second source of energy after carbohydrates. As well as the storage of glucose, triglycerides can also be formed from the digestion of fatty foods into the base components glycerol and fatty acids before subsequent absorption.

So how exactly is fat managed?

Well, to start with there are two different kinds of adipocytes, white and brown. It is important to distinguish between these two cell types as they have very contrasting roles. When fat is said to be 'stored', it is held within the white adipocytes of the body. When these cells are content with the amount of glucose needed to carry out respiration to yield the maximum number of ATP's, excess glucose is converted into fat here. The receptor that recognises this and promotes the storage of fat is called PPARγ. Conversely, brown adipocytes are considered extremely 'energy ineffecient', "burning" up triglycerides and storing very little, if any, of them. The result is that much heat is produced, a consequence of the many mitochondria this cell has. In fact, it has the most of any cell in the human body. This was once considered a survival mechanism for newborn infants as they had brown adipocytes in large numbers - the heat generated helps to protect the child from comparatively cold conditions to the womb. New research has found that adults posses these exact same cell types, 'roughly 60g in the neck region'. These cells adjust their calorie-burni ctivity in accordance with food intake and external temperature just to name a couple.

Now here is the intriguing part. Recent experiments in mice have shown that an increase in brown adipocytes 'help protect against diet-induced obesity and type 2 diabetes by preventing the build-up of triglycerides in other cell types, such as those in the liver and muscle'.

So what are the potentials of brown adipocytes?

In my view, adipocytes quite fasdcinate me now I've read a lot more into the subject. In cellular respiration, glucose is commonly processed through a series of step-by-step exothermic reactions. However in brown adipocytes, the stage that normally produces the largest number of ATP's is halted. It is known as oxidative phosphorylation. This means rather than using the energy released form the exothermic reactions to produce ATP, it is dissipated as heat energy - usually regardedas very inefficient!

Scientists have spent years of research trying to suggest new methods to combat the ever-pressing problem of obesity. Novel resserach into a particluar protein found in adipocytes called sirtuin has sparked a glimmer of hope. Sirtuin has been found to be associated with 'calorfic restriction' where life expectancy has increased with decreasing the number of calories in the diet gradually over a prolonged period of time. As sirtuin is commonly found in metabolising brown fat cells, there may be potential for sirtuin to be stimulated in white fat cells in combating weight gain. The experiments that scientists carried out confimred that with an increased presence of sirtuin, white fat cells started to show some of the characteristsc of brown fat cells, i.e. genes were becoming switched on that were analogous to brown fat cells. Parallel to this, other genes in the white fat cells were becoming switched off, again the same ones that are switched off in normal brown fat cells.

This phenomenal "growing" effect of white fat cells has significant potential. It is down to the protein sirtuin, how this works requires a little more understanding. Sirtuin is found to bind to the PPARγ receptor and modifies it. This receptor is found on the nucleus of white adipocytes. Therefore this receptor doesn't resume in normal function - instead it 'activates a transcription factor called Prdm16 that stwiches on a set of genes necessary for using up chemical energy to produce heat'.

Another plus side of the 'browning' of white adipocytes is that, in diabetic mice, their responsiveness  to insulin increased.

Is it all too good to be true? Well, not exactly. You see, sirtuin is found in many different types of cell throughout the body, not just adipocytes. This would imply that adjusting concentrations of sirtuin will have additional, even unwanted effects to the body. These problems will need to be investigated further by researchers in the future.


Credit to Joseph Robertson, who writes for the Biological Sciences Review (Volume 26, Number 2), for his article "Fighting the Flab" which was published.

Treating Brain Tumours With Proton Beam Therapy

What has been highlighting the news recently is the Ashya King case and the implications of certain therapies to treat brain tumours. Ashya King is the five year old son of parents Brett and Naghemeh King. Whilst Ashya was being treated in a UK hospital, his parents, without consent from doctors, took him from hospital and journeyed overseas to seek the treatment they wanted for their son. Mr and Mrs King were in preference for proton beam therapy for their son - this directly targets cancer cells and is considered to have less side effects than the conventional radiation/X-ray therapy. However currently in the UK, proton beam therapy isn't available for the treatment of tumours like Ashya has -  instead it has only been used to treat certain eye conditions. Government legislation says that proton beam therapy will be introduced in combating cancers like Ashya has by 2018. Understandably, Ashya's parents simply cannot wait that long for the treatment; it is important to intervene as early as possible when tackling a tumour as severe's as Ashya's.

What is proton beam therapy?

X-rays have long been used to treat cancerous tumours. Given in sufficiently high doses, X-rays will be able to kill tumour cells, however what many people view as a fundamental flaw is that healthy tissues can be exposed to similar intensity radiation. This leaves risk of healthily tissue being destroyed which can in turn be potentially detrimental to health. Therefore many people believe proton beam therapy to be the best option, as even in high concentrations there is greatly reduced damage to healthy tissues (and more importantly, the vital organs). The problem that arises is that those receiving X-ray therapy will receive a lesser dose than desired by doctors as the risk to healthy tissue comprises the treatment. Many patients desire proton beam therapy partly because of this.

Recalling fundamental chemistry, protons are subatomic particles of the atom which are positively charged. They have a relative charge of +1. Opposing this, 'orbiting' electrons have a relative charge of -1, and thus the two subatomic particles have an attraction for each other. Having this rather basic intuition allows us to make sense of how proton beam therapy works. As charged particles, such as protons are fired near other molecules or atoms, they become attracted to the elections with orbit the atoms. This causes the atoms to ultimately lose electrons and as a result become positively charged. These are now ions. Obviously, this process is therefore called ionisation which causes the chemical properties of that atom to change. This is vitally important when targeting cancer cells. As the proton beam targets the cells, the molecules within those cells become damaged, or ionised. However it matters what molecules become affected, for example to damage the DNA of a cancer cell means destroying it's functionality. As a result, key processes such as mitosis (cellular division) and DNA replication become disrupted. With a high enough dosage, no matter how hard enzymes work to repair the damage, their efforts become futile. Cancer cells have less capability of repairing damage to organelles and molecules than healthy cells, which means minimal concern for the normal cells that are bombarded with the proton beam. Fundamentally, the proton beam creates a selection pressure on cancer cells, they are more likely to be destroyed and subsequently their numbers decline. 

Although both X-rays and proton beams aim to target cancer cells, it is considered that the precision and accuracy of the proton beam is greater. The 'distribution of protons can be directed and deposited in tissue volumes'. Another downfall with X-rays is that as they 'lack charge and mass', their use results in radiation being deposited 'in normal tissues near the body's surface'. This ultimately poses a risk of genetic mutation to healthy cells.

Interestingly, protons can be accelerated or decelerated as and when required - X-rays cannot be 'energised to specific velocities' unlike protons. This property of protons allows physicians to have some element of control as to how penetrative the proton beam is. As a very physical entity, protons slow down as they penetrate further into tissue, coming into contact with more electrons as a result. It follows that as the protons decelerate, they eventually stop at their designated site - the cancer cells. This is not the case with X-rays as some radiation is left to pass through the tumour tissue and through to other healthy tissue via an "exit dose" before exiting the patient completely.

I have empathy as to why the parents of Ashya want to pursue this proton beam therapy. With fewer side effects and less damage to normal tissue, it is highly likely that Ashya would enjoy 'a better quality of life during and after proton treatment'.


Credit to the BBC on their updates on the Ashya King case and to The National Association for Proton Therapy for their article 'How Proton Treatment Works'. Read more on the subject here.

Image: Patient receiving radiation therapy - BBC

Understanding Congenital Heart Disease

The heart is undoubtedly to many one of the most essential organs of the body, supplying all major tissues with oxygen and glucose which allows body cells to respire - to generate ATP. However what is also very important is how the heart develops during pregnancy, and how effective it is as an organ. Unfortunately children are sometimes born with congenital heart defects which means the heart's duty to pump blood around the body sufficiently can become compromised. These conditions are considered relatively rare which means for scientists, students, doctors and specialists, heart development has become a very interesting topic of study. Since the heart is considered a relatively complex organ, giving rise to our double circulatory system, rare conditions help scientists to appreciate it's development. More crucially, it may trigger the development of new treatments for these defects. An article in the Biological Sciences Review helped me understand what exactly we mean by congenital heart disease.

To start with, an interesting statistic you may want to bear in mind is that 'between 1% and 5% of the human population are born with structural or functional problems with their hearts'. You may consider this a small percentage, but this equates to a very large quantity. But a statistic isn't always representative - many congenital heart defects in infants aren't detected which means the actual percentage could be higher. What is even more interesting, is that congenital heart disease is the 'most common non-infectious cause of child death'.

The tree main types of congenital heart disease which you would want to know about are:

• Septation defects: This is where there is an error is the separation of different parts (chambers) of the heart
• Unilateral blocks: Defects referring to the heart valves
• Routing abnormalities: Erros in connecting chambers of the heart with the correct major blood vessel or even failure in connection at all. 

How does the mammalian heart form? First of all, it's important to appreciate how blood is pumped around the body in a fully developed heart. Here I've included an animation which shows how this is achieved. Notice the valves are incredibly important in monitoring how blood flows and it's volumes whilst in the four chambers. Credit is given to The Children's Hospital of Philadelphia for this animation.

As the heart is the first organ required of an embryo, it develops quite early, starting as a 'crescent-shaped structure at about 2 weeks of gestation'. From this, a straight tube structure takes form which leads onto a Y-shape tube due to a join which forms at it's centre. What is amazing is that even at this stage of development, the heart continues to beat 'as early as day 22 of gestation'.

The next phase of development includes determining the positions of different parts of the heart. Chambers need to be positioned in the correct places relative to each other. This is what is known as "cardiac looping", and involves the heart muscle to bend in a very particular manner which is controlled by genes. This stage of heart formation is crucial as malformations can lead to routing problems when blood vessels may fail to attach to the various chambers of the heart.

After this stage, chambers need to be formed. At around 6-8 weeks into pregnancy, atria and ventricles become separated from each other as different areas of heart tissue become distinguished. At this point, valves are also formed in conjunction with the chambers. You may have heard of a 'hole in the heart', when someone has a hole through their atrial septum. This condition can arise at this stage of development. What is intriguing is that despite this seemingly worrying condition, problems don't seem to arise until adulthood (it is asymptomatic). It is the most common congenital heart defect diagnosed in adulthood. Of course it would be better that this was diagnosed sooner, however as mentioned many heart defects go unnoticed during early childhood.

However this isn't always a bad thing, not in foetuses that is. Foetuses contain specialised structures in their heart which aid development which adults do not possess. The foramen oval is in fact 'a small gap through which blood passes from the right atrium into the left atrium'. Why is this? A foetus is supplied blood which is oxygenated from the placenta, from the mother. Therefore if this blood were to pass through it's lungs it would render them useless as the blood is already oxygenated. This means in a foetus, the right atrium receives oxygenated blood which can then be passed into the left atrium and then the left ventricle to be pumped to the rest of the body. This gap normally closes shortly after birth, however if this fails this is an alternative way a 'hole in the heart' can remain. Surgery is usually used to treat the condition.

How can we treat heart defects? In order to pursue a treatment, we must start with extensive and long-lasting research into the genes and signalling pathways used in heart development. Scientists have started to examine heart defects that have been induced by specific mutations in genetic code, in DNA. As a single gene codes for the production of a single polypeptide, a change in phenotype can be deduced from a change in the genetic sequence, or genotype.

Scientists have introduced a method of identifying what processes regulate heart formation - this is called mutant screening. There are two possible ways of carrying out this method:

1. 'Forward genetics' - Individuals are studied for a particular characteristic, or phenotype. Then their genetic sequences are analysed in the hope of identifying the gene responsible for a particular abnormality. 
2. 'Reverse genetics' - This is considered the converse approach, where the effect of a known gene on a characteristic is investigated. In mice, this could involve deliberately inducing a mutation (using a mutagen such as ENU*) or removing a gene to see whether this causes a change in development. Removing a gene means no longer synthesising a particular protein, so this is useful when looking at how the heart develops without that protein present. 

*ENU = N-ethyl-N-nitrosourea (causes a point mutation)

An example of this which is stated in the article is that of the gene Nkx2.5 in mice. The removal of this in mice caused faulty development. However when looking at mutations of this gene in humans, it correlated with atrial septal (hole in heart) defects in families. Another example is that the loss of protein TBX1 encoded by a certain gene leads to certain congenital heart defects in humans. 

The potential of genetic screening for heart defects is fast advancing. It has allowed us to screen embryos for diseases and in the future could mean correcting abnormalities during pregnancy.

Max Brödel inspired anatomical drawing of the heart, showing ventricular and atrial chambers.

Credit is given to Katherine Powell who writes for the Biological Sciences Review (Volume 26, Number 1) for her published article . 

Whole Functional Organ Grown In Animal

It's always exciting to hear new 'world firsts' in the medical world, what caught my eye recently was that new strides were being made in the area of organ synthesis. An article from the BBC caught my attention. For the first time, a functional organ has been successfully grown inside an animal. Now you may have heard before of organs being synthesised in the laboratory environment, outside a living body. However that has changed. Scientists at the University of Edinburgh encouraged a group of cells ti develop into a thymus gland. The thymus gland is a notable part of the immune system where T-cells mature and grow. T-cells are part of a much larger operation when fighting disease and foreign microbes. The results for the study were published in the scientific journal Nature Cell Biology. The cells were implanted into mice, which then proliferated in number and took shape to a thymus gland.

But where did the cells come from? In fact, scientists were able to use mouse embryonic stem cells which were multi-potent. This useful property allows scientists to re-programme cells to develop into almost any type. The specificity of a cell which needs to be cultured is very important when developing a particular organ.

It is important to realise that this study is still in its early stages, and only with vigorous testing and further research will scientists be able to trial his technique on humans (or human tissue). Problems are likely to arise with regenerating organs, such as the fear of rejection from the patient. After all, embryonic stem cells were used - in patients adult stem cells would be more desirable to avoid rejection. Additionally scientists will need to be wary of the fact that the cells could divide uncontrollably to form a cancer.


Some have called this study to be analogous with one breakthrough last year when a brain the size of a human foetus's was synthesised. However to implement the brain into a living body proves very difficult, however the thymus can be seen as a simpler organ to replicate which is why it was used in this study. For example, the thymus is essentially a mass of tissue, it isn't divided into separate chambers like the brain. The only two main regions are the cortex and the medulla. (Wikipedia article - Thymus)


In my view, this step proves to be the start of a new age of regenerative medicine. Replicating one organ raises the obvious question: Can we make any organ? Theoretically, yes. However I imagine every organ has it's own problems when attempting to sculpt it's shape. Organs such as the heart and the stomach have intricate contours and a specific shape to their function. The rugae on the stomach lining contribute to a larger surface area for digestion for example.

An interesting point in the article was made about the potential of the findings. Where can a newly grown thymus be most useful in our society. In Britain, and perhaps in other parts of the world, there is an increasingly ageing population. Growing new thymus glands or simply thymus tissue, could be used to replace the ones of the elderly. It is known that with old age, the immune system tends to weaken partly due to the shrinking of the thymus.

As I have mentioned, the field of regenerative medicine has advanced at an alarming rate. Already, patients have been the recipients of newly grown tracheae, and blood vessels. This has been achieved so far by 'seeding' patient cells into a scaffolding which then slowly disintegrates over time to leave developed tissue.

But is this better than organ transplantation? Dr Paolo de Coppi of Ormond Street Hospital suggests "Research such as this demonstrates that organ engineering could, in the future, be a substitute for transplantation."


Credit to James Gallager, Health Editor for the BBC for his article which can be read in further detail here

The History of Anaesthesia!

Recently I undertook some work experience at Leicester Royal Infirmary, where I learned about the roles and duties of not just doctors, but also of the many people that make up a surgical team, and those who accompany consultants in their work. On the first day, I remember the consultant anaesthetist I was shadowing in the MRI scanning unit was very enthusiastic about the field he works in. In fact he was so committed to informing me what exactly anaesthesia is, he gave me a two hour lecture on the history of anaesthesia! After all, MRI scans can take unto 40 minutes which left us plenty of time to discuss aspects of medicine and indeed how anaesthetics came about in today's medical world. I must admit, it was very interesting and I thought it would be fitting to talk a bit more about it here.

Well, fundamentally we need to understand what exactly is an anaesthetic. General anaesthetics are 'medications used to cause a loss of consciousness' according to NHS Choices. It is widely accepted that these drugs interrupt the transmission of signals along the nerves of the body. This explains why during surgery, the presence of an endotracheal tube in the throat fails to initiate a 'chocking' reflex by the patient. Anaesthetic drugs can by administered in one of two main ways: intravenously in a liquid (through a cannula), or as a vapour through a breathing mask. It is generally known that using a needle and giving the anaesthetic by injection is a lot quicker and 'smoother'. However using the vapour is a very suitable option if one is not comfortable around needles or the idea of injection.

In today's medical world, anaesthetists have access to quite a diverse array of anaesthetic drugs such as desflurane and isoflurane (in combination with nitrous oxide). Conversely in the 17th century, between 1835 and 1845, there was evidence that people attempted to use anaesthetic agents. Despite these formulations, these drugs didn't have a significant effect on the medical field at that time. Back then, it was William Morton who administered the first anaesthetic made of ether - this was a medical breakthrough. The patient, Gilbert Abbott received the anaesthetic on the 16th October 1846, for treatment of his jaw where a lump needed to be surgically removed. This took place in the Massachusetts General Hospital, in Boston. After this pivotal event, ether anaesthetics were increasingly becoming used in hospitals for surgeries including amputation and tooth extraction. For surgeons at least, this new revolution was considered a step forward. In those times, the diversity of surgery was quite limited compared to what it is today. Previously, operating on the head for example was especially avoided. Patients were conscious after all, awake if you like. Strapped down to the table, it was known many would faint at knowing their leg would simply be cut off, or at the sight of a newly sharpened knife. I'd like to share one of the terrible stories of early surgery that was originally published in the New York Herald, 21st July 1841. I managed to find this excerpt from The Royal College of Anaesthetists webiste.

"The case was an interesting one of a white swelling, for which the thigh was to be amputated. The patient was a youth of about fifteen, pale, thin but calm and firm. One Professor felt for the femoral artery, had the leg held up for a few moment to ensure the saving of blood, the compress part of the tourniquet was placed upon the artery and the leg held up by an assistant. The white swelling was fearful, frightful. A little wine was given to the lad; he was pale but resolute; his Father supported his head and left hand. A second Professor took the long, glittering knife, felt for the bone, thrust in the knife carefully but rapidly. The boy screamed terribly; the tears went down the Father’s cheeks. The first cut from the inside was completed, and the bloody blade of the knife issued from the quivering wound, the blood flowed by the pint, the sight was sickening; the screams terrific; the operator calm."


Reading this re-emphasises for me how fortunate we are to have access to anaesthetic drugs for surgery - especially very invasive ones. To great appreciation of the surgeon, they could afford to be more accurate, precise and careful when performing operations to get the optimum result. Now the 'doors were opened' to many other parts of the body such as the brain that could now be safely operated on. But surgery improved not only with anaesthetics, but with the introduction of sterile surgery catalysed by Joseph Lister in the 1860's. Lister used methods of cleaning and dressing wounds with a solution of carbolic acid which saw a decrease in patients suffering gangrene post-surgery. Even the idea of surgeons wearing clean gloves was down to Lister as well as the sterilisation of surgical instruments, much like today. 
A year later after the introduction of ether anaesthetics, different agents that could be inhaled were formulated - one example being Chloroform. This was first used by James Simpson, Professor of Obstetrics in Edinburgh. However there were a few known flaws of this particular agents. One surprising effect was that usually in very nervous patients, sudden death could occur (1848 saw the first events). Another was that it could induce late-onset liver damage. Despite this, it proved quite popular due to it's ease of use and effectiveness. 
Soon enough, many different anaesthetic agents were being used, even cocaine became useful as a local anaesthetic from 1877! By the early 1900's, minimally toxic anaesthetic drugs were being used.
It is important to realise however that anaesthesia doesn't just pay attention to the drug that is given to a patient. Whilst on my work experience, I learned that the anaesthetist in the theatre has a very important duty to monitor the patient's holistic condition: their breathing and if they are experiencing any pain are two main examples. Endotracheal tubes that could be placed into the mouth and descend into the windpipe was the next invention that would become increasingly used in the 1920's and 1930's when the techniques became perfected. Furthermore, you may be surprised to hear that intravenous methods of delivering anaesthetic didn't come about until the 1930's - this helped deliver the drug smoother and quicker, as well as being more pleasant for those who detested the more traditional inhalation agents. Even more progression came about when muscle relaxants such as curare (actually a poison!) became more and more useful over the course of the 1940's and 1950's. Despite all these advancements, what anaesthetic that is considered in today's world a revolution is halothane. Apparently much easier to use and therefore more practical, it is probably the most widely used category of anaesthetic. Since the mid-1950's, this group of agents have improved in potency and become safer after years of refinement. 
With the probability of mortality of less than 1 in 250,000 from taking an anaesthetic, it is comforting to patients that anaesthesia in the modern age is considered very safe. This is indeed one area of medicine that I have become so interested in recently - reading about it's history is especially useful as well as knowing how it has evolved as a field over the last 150 years. 


More information on what anaesthesia is can be found on the NHS Choices website here.


Full credit is given to Dr D J Wilkinson, past honorary treasurer of The Royal College of Anaesthetists who gave permission for an article to be published on The Royal College of Anaesthetists website titled "The History of Anaesthesia". To read in more detail about what I have talked about, you can see the original text here.

The Complications of Obesity And Their Devastating Effects

What is becoming increasingly common in western countries such as the UK is the onset of obesity. Some would say that it has dominated health related news for the last few years. Following this, increasing numbers are likely to result in increasing concerns. What many people associate with obesity is the increasing risk of developing heart related diseases and the early development of diabetes. However what many people fail to realise is that obesity is becoming increasingly related to many different cancers. Although all these diseases could be considered equally devastating, the spread of cancer and it's effects is the cause of many funded research projects throughout the world. It is indeed of the worlds emergencies.

According to an article published in the Lancet medical journal, obesity has the potential to put people 'at greater risk of developing 10 of the most common cancers'. The study has arrived at this link through investigating the health of 5 million people which is an incredible number for a study. Additionally these people were monitored over an extended period of 7 years, which is very comprehensive in my opinion. It follows that I have increased confidence in the findings due to the sheer scale of the study - however it is always important to understand the study holistically before drawing conclusions.

It is fair to say that obesity can increase the risk of developing cancer in general with age. However what was unique about this study was that the size of a risk is dependent on the type of tumour. For example, the study found that cancer of the uterus carried the biggest risk when an individual becomes obese. Conversely leukaemia carried the lowest relative risk. Obviously men will not suffer from cancer of the uterus, so the biggest risk that is posed to obese men is gallbladder cancer, according to the study.  Scientists from the London School of Tropical Medicine found that 'each 13-16 kg of extra weight an average adult gained was linked firmly and linearly to a greater risk of six cancers'.

Furthermore, a high Body Mass Index (BMI) has been linked to higher risk of the incidence of cancer of the liver, colon and ovaries just to name a few. However what was very peculiar is that the researchers found that an increased BMI seemed to be linked with a decreased risk in prostate cancer. Of course, this only displays a correlation which doesn't always necessarily indicate a causal link, nevertheless this statistic is intriguing. Despite the links to risks with BMI, one may assume these links are sufficiently linear. But according to Dr Krishnan Bhaskaran who led the research team, "There was a lot of variation in the effect of BMI on different cancers". An example he described was that the risk of cancer of the uterus increased 'substantially' with increased BMI however this link proved more 'modest' when looking at other tumour types.

So it is evident that scientists will need to investigate the causal mechanism behind the differences in increased risk. Dr Bhaskaran suggests that "BMI must affect cancer risk through a number of different processes, depending on cancer type". Although quite vague, this statement enforces that cancer is an area of research that will need to be fully understood in the coming years in order to cause medical advances in the scientific world.



Credit to Smitha Mundasad, BBC News Health Reporter for the original article. Read more on the subject here.

Could the Ebola Virus Reach The UK?

This year one of the biggest stories in heath news and in fact world news is the outbreak of the Ebola virus. Notably, this outbreak has seen the biggest surge in infections and fatalities in human history. The Ebola virus is known to cause the most unpleasant of symptoms, from vomiting and fatigue to bleeds from the eyes and nose ('internal and external bleeding'). As of 27th July 2014, the virus has claimed the lives of 660 people in areas with weak healthcare systems such as Sierra Leone and Liberia. The high mortality rate of around 90% shows how potent the virus really is. Even healthcare staff clothed in complete overalls have been known to be infected. Currently there is no cure for the disease - the only appropriate action for healthcare services is to isolate the infected and transfer them into intensive care.

The UK foreign secretary Philip Hammond has described to the BBC that this outbreak is a "threat" to the UK. Very urban areas in sub-sahrhan African countries have been the most affected, so perhaps the virus could strike an impact in the UK or other Western countries with built-up areas.

The virus is able to be transmitted through bodily fluids and faecal matter, it means the virus can be contained more easily than airborne diseases in areas where people are in close proximity of each other. One of the most discussed environments for the virus to be transmitted in passenger planes. Commercial flights will only carry a few toilet facilities for passengers to use. It follows that there is a risk many people could become infected through use of one toilet facility.

Recently, it was reported that one man from Liberia who showed signs of the Ebola virus was permitted to board a plane to Nigeria. Nigeria hadn't reported any cases of the virus up until the man arrived in Nigeria and died shortly after in a isolation ward due to infection. It is even confirmed he vomited whilst on the plane, and despite having 'high fever', he boarded the flight.

So how is this outbreak being 'controlled'? As mentioned, the infected will need have an accurate diagnosis followed by isolation in hospital. This is primarily to reduce the chances of the virus claiming another host. Appropriate sanitation will also need to be ensured to minimise the exposure of bodily fluids or faecal matter to the environment.

In my view, an outbreak in the UK will be able to be controlled more effectively than in less equipped areas in Africa. Also higher standards of sanitation and healthcare would mean reduced risks of transmission between individuals.


Credit to Adam Withnall and Tomas Jivanda who write for The Independent. Links to articles in The Independent:

Published 26th July 

Published 27th July

Published 30th July

The Ongoing Pursuit For Stem Cell Medicine

In recent times, attention has been drawn to a particular area of biological science involving the use of stem cells. In biology, these are a type of undifferentiated cells which are capable of being multipotent or even pluripotent (embryonic stem cells only). This truly remarkable characteristic has intrigued and ultimately inspired scientists to develop techniques that can be applied to the medical field.

However we must appreciate that there are two types of stem cell. Adult and embryonic. Embryonic stem cells are derived from a 'small hollow ball of cells' called a blastocyst. This is one of the immediate results of fertilisation. What scientists are interested in is the inner cell mass - these cells are undifferentiated but more importantly they are pluripotent. This means that they have the capacity to develop into any type of cell in the body. Conversely, adult stem cells are considered multipotent, meaning they have the capability to develop into one type of cell however the variety is limited. In the human body, the most common extraction point for adult stem cells is bone marrow (although many other tissues and organs are known to produce stem cells, including the brain, heart and skin). Interestingly, foetuses have also been found to have stem cells.

Some adult stem cells such as fibroblasts can actually be reprogrammed genetically for them to 'behave like embryonic stem cells'. These are known as induced pluripotent stem cells.

Another fascinating property of stem cells is that during asymmetric division, two daughter cells are produced with contrasting characteristics. One cell is the result of self-renewal, whilst the other the result of differentiation. This explains how our body is able to heal and repair itself - any type of cell can be made available to any site where it is needed. This ability for these cells to replicate themselves and differentiate is a marvel of genetics. So how is this controlled? An engaging article in a Biological Sciences Review magazine gave me an insight.

Differentiation of stem cells is dependent on 'changing the expression of the self-renewal and pluripotency control genes'. Scientists have carefully monitored which genes switch on or off during differentiation for a variety of cell types. The result is, we can identity which genes control differentiation for a vast array of cell types. An example given is that for the production of cartilage cells (chondroctyes), adult stem cells need to 'express high levels of the gene SOX-9. This gene encourages the expression of a different gene called COL2A1 as a consequence. As genes code for polypeptides, it follows that COL2A1 codes for the production of the type-2 collagen protein. Cartilage largely comprises of this protein.


When adult stem cells are used in medicine, scientists tend to use induced pluripotent stem cells (see above) as their diversity for differentiation is a significant advantage. However for medical applications in the body, sometimes we require the aid of biomaterials to supplement the use of implanted stem cells.  The example used in this article is treatment of back pain due to a slipped disc. The pain is caused by an indentation into the spinal cord by a disc, causing a compression. Intevertebral disc cells are produced by stem cells in a lab, which can them be cultured and left to proliferate. One approach to treating the condition is to 'seed' the cells into a synthetic hydrogel. This compound exists as a gel at body temperature, it is also thermosensitive. This gel can then be 'injected into the damaged disc, where it would form a gel and act like a shock absorber, similar to a natural disc'.

The potential of stem cells in medical application is exciting and promising with continuous ongoing research. Diseases such as Alzheimer's and muscular dystrophy could one day be in combat with emerging stem cell treatments to improve the lives of those who endure the pain of these conditions.


Credit to Dr Stephen Richardson, lecturer in cell tissue engineering at the University of Manchester who wrote for the Biological Sciences Review (Volume 26, Number 4)

New Assisted Dying Bill in Review

One of the latest news stores this week is the review of the assisted dying bill, which if passed will give permission for doctors to administer doses of powerful drugs to end the lives of those whose quality of life is seriously compromised. Essentially euthanasia, this will allow people who are seriously terminally ill to consider whether they would want to sustain their lives any longer. For me, this is a topic in which people should approach with caution as it is real lives, real people, real stories that we are dealing with.

On a basic level (although I respect this isn't a simple topic at all) we are evaluating the quality of a persons life against the longevity or quantity of their life. Indeed it leaves the nation divided in opinion. Speaking to The Independent, oncologist Professor Karol Sikora  believes that the implementation of this power for doctors will result in "death squads" of doctors.

What is important to note is that assisted dying will be of significant relevance to the terminally ill who have been told the have 'less than six months to live'. If this bill is passed, it will mean doctors will have a further big responsibility, more vitally important choices to make.

Doctors in my opinion may only make up a fraction of this matter. In medicine, the patient is the paramount figure of every case - ultimately it is their choice whether to end their own lives or not. I believe they should have the choice, providing they are sane and in "the right frame of mind". No doubt, their families will have a part to play in every patient's decision.

However British Prime Minister David Cameron is concerned that if passed, the bill may cause people to be "pushed into things that they don't actually want for themselves."

Some may argue that assisted dying will help to suppress the needless suffering of the terminally ill - this could have an effect on families as well will lessened responsibility and emotional suffering perhaps.

What do people think? Well according to a 'poll for ITV this week, 70% of Britons are behind the assisted dying bill, with 10% disagreeing'.

In my view, I believe that the bill should be passed. The attention must be brought to the patients themselves. It is they who endure terrible suffering, it is they who should be given a choice.

Credit to Natasha Culzac, reporter for The Independent for the original article. Click here for more on the story.