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.
Monday, 24 November 2014
Sunday, 16 November 2014
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'.
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
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
Wednesday, 5 November 2014
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.
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)
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)
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