Antibiotics; A journey from good, to bad, to ugly

As I hope you are already aware, medicine is facing a crisis at the moment which could prove to be a bigger killer than cancer; antibiotic resistance. Bacterial infection seems an archaic issue, one that we solved years ago and have since forgotten as a major threat to human health in the public eye, but it’s making a comeback. Before we get into all that, however, let’s first look at what antibiotics are and how they came about in the first place.

Antibiotics are a group of drugs which can treat or prevent bacterial infections by inhibiting or stopping the growth of bacteria. There are hundreds of different antibiotics in circulation today, but they all stem from just a few drugs so can be categorised into six groups. One of these groups are the penicillins, which include the drugs penicillin and amoxicillin and this is where the antibiotics’ journey begins. Penicillin was discovered in 1928 by Alexander Fleming and is generally thought of as the world’s first antibiotic. Its initial discovery is quite well known, with Fleming accidentally uncovering the antibacterial properties of a mold called Penicillium notatum when returning from a holiday to find that where the mold had grown, normal growth of Staphylococci was prevented. Fleming then grew some more of the mold in order to confirm his findings; he had discovered something that would not only prevent growth but could be harnessed to fight bacterial infection, changing the world in its wake. However, Fleming didn’t develop Penicillin into what it is today. To do this, the active ingredient would need to be isolated, purified, tested and then produced on a grand scale.

It was 10 years later that endeavours into this began, when Howard Florey came across Fleming’s work and began further developing it with his team at Oxford University. Florey, and one of his employees Ernst Chain, managed to produce penicillin culture fluid extracts. From this, they experimented on 50 mice that they had infected with streptococcus and treated only half with penicillin injections. Whilst half of the infected mice died from sepsis, the ones which had been treated survived thus proving the effectiveness of penicillin. In 1940 the first human test was conducted, with injections being given for 5 days to an infected Albert Alexander. Alexander began to recover, but unfortunately Florey and Chain didn’t have enough pure penicillin to completely treat the infection and so Alexander ultimately died. This was now their biggest problem; making enough penicillin. It took 2,000 litres of culture fluid to extract enough pure penicillin to treat just 1 human case, so you can see how treating an entire population would frankly be impossible if they continued in this way. It was in the US whilst Florey and Chain were looking to find a solution to this problem that they happened upon a different, more prolific fungus called Penicillium chrysogeum. This yielded 200 times more penicillin than the previously used species, and with a few mutation-causing X-rays yielded 1000 times more. This allowed for 400 million units of penicillin to be produced for use during the war in 1942, reducing death rate from bacterial infection to less than 1%. And so began the antibiotic revolution in medicine which changed the world into what it is today.

Now, over 70 years later, we’re faced with a huge issue. Bacteria have become resistant to antibiotics due to their overuse. Antibiotic resistance occurs when a bacteria mutates so that the antibiotic can no longer kill it, and is part of natural selection. However, from previous knowledge of natural selection you might know that it is slow process across many generations and relies on the mutation being an advantage in order for it to become widespread. Yet when you use antibiotics rather than having 1 mutated bacteria amongst millions of non-mutated, all non-mutated bacteria are killed leaving a 100% resistant population. Albeit that population is exactly 1, but bacteria can multiply and start causing havoc very quickly. And then those same antibiotics no longer have any effect on the new culture, leading to longer hospital stays, more expensive medication and increased mortality rates.

Given how easily everyone is now able to travel around the world, this issue is not just localised to 1 country or continent but is on global scale. Given that tackling antibiotic resistance requires investment into finding new antibiotics and using the more expensive medications that are on hand, developing countries could be hit much harder than developed. Meanwhile, our struggling NHS will experience even more pressure as patients have longer stays at hospital. Worst-case scenario, if this issue isn’t addressed we could be returned to a time before antibiotics where common infections are once again fatal, killing 10 million people a year by 2050. Clearly not a desirable outcome, so how can we tackle antibiotic resistance?

Prevention and control of antibiotic resistance requires change at several different levels of society. The World Health Organisation has made recommendations for what we as individuals, healthcare professionals, policy makers, and people in the agriculture sector. Amongst the advice for individuals is not sharing leftover antibiotics, not demanding antibiotics if they aren’t considered necessary and preparing food hygienically to prevent infections. Meanwhile the healthcare industry needs to invest in research into new antibiotics, as so far most drugs being developed have only been modifications to existing antibiotics. They don’t work for long, and of the 51 new antibiotics currently being developed only 8 of them have been classed by WHO as innovative and capable of contributing meaningfully to the issue.

Research into new drugs is of the utmost importance, but the responsibility appears to fall to governments to fund such research as pharmaceutical companies are reluctant to do so. Some suggest that this is because it is more lucrative for drug companies to treat chronic conditions in which patients rely on their drugs for a lifetime than providing short-term (and may I point out, life-saving) treatments. Thankfully, this year countries including Switzerland, South Africa and the U.K. pledged a combined $82 million to support the Global Antibiotic Research and Development Partnership which was set up by WHO and the Drugs for Neglected Diseases Initiative. Less encouraging, is the estimation by the director of the WHO Global Tuberculosis Programme that more than $800 million is needed annually to fund research into new anti-tuberculosis medicines.

I know. It’s feeling dismal. But what can we do, on the metaphorical shop floor? Stop the overuse of antibiotics, follow through on any prescribed courses of antibiotics even if you’re feeling better and make other people aware of the issue. The bigger the issue becomes in the eyes of the public, the better the government and other organisations will address it so talk about it to anyone who will listen! I am optimistic that we as a species will survive this most recent challenge to our health, but only if we start pulling up our socks and addressing the situation.

 

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“Science has been a process of continuous advancement towards objective truth”

This is one statement from which I wrote an essay for, in a past paper for the BMAT. The BioMedical Admissions Test, alongside the UKCAT, is one of the medicine admissions tests that medical schools might ask for and consists of 3 sections: Aptitude and Skills, Scientific Knowledge and Applications and a writing task. Unfortunately, pretty much the only way to prepare for either admissions test is practice, practice, practice so I decided to share one of my practice writing tasks with you….

 

This statement suggests that developments in science have all, always been working towards the discovery of a set of unchanging and unbiased facts. It suggests that the goal of all science is eventually to uncover these facts that have been consistent throughout mankind’s scientific journey. For example, the ‘discovery’ of gravity by Newton. Gravity has been around and affecting us always but only became apparent relatively recently, and cannot be denied or manipulated.

However, it can be argued that advancements in science have not been continuous, as we have had periods of rapid advancement followed by periods of stagnation often due to the limits of technology preventing further advancement. For example, the improvements in the microscope allowed for the Germ Theory to be discovered consequently. Sometimes, incidentally, stagnation was not brought on by technological limits but by limits to scientific advancement out of fear such as the Church historically discouraging new theories and discoveries of Galileo’s out of fear that they would challenge their teachings.

What’s more, it can be argued that the truths we work towards discovering are in fact not objective, nor as they unchanging as the statement might suggest. This ‘objectivity’ supposes that scientific fact is not affected by societal influences however I would argue the contrary, as the way those truths are perceived very much depends on when in history they are discovered and the state in which society is in at the time. Moreover, the scientific truths have not and will not always be the same as science is not as constant as it may seem. Facts are constantly changing, for examples evolution drives changes and adaptations in organisms, the universe is constantly changing with its expansion and the emergence or disappearance of stars.

The truths that science offers are always changing slowly but surely so that we are not working towards the same truths they may have worked towards a millennia ago an for this reason I cannot agree with this statement. Whilst science is about advancement, it is not always continuous and the truth is not objective.

 

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‘Carbon dating’ cancer? What’s that all about?

Last week, the Institute of Cancer Research announced that scientists have been able to precisely pinpoint the timing in which different stages of a patient’s cancer developed. This could result in some interesting progress in the treatment and understanding of cancer and I will explain how researchers are doing this, but first- what is cancer?

Cancer is a group of diseases caused by the uncontrollable division of damaged cells. Cells can become damaged in this way due to a mutation in their DNA which intervenes with the regulation of mitosis (cell division). More specifically, the genes proto-oncogenes and tumour suppressor genes can become mutated. Proto-oncogenes trigger division, however mutated ones (known as oncogenes) trigger mitosis to happen at a much faster rate than normal. Meanwhile, mutated tumour suppressor genes fail to inhibit cell division as they should. Both mutations, as you can imagine, lead to the fast and furious growth of a cell into a tumour.

Mutations naturally occur quite frequently, but not all mutations cause cancer, and in fact it often requires more than one mutation in a cell in order for it to become cancerous. Most of the time either the mutation is relatively harmless, the DNA is repaired or the cell ‘kills itself’ before it can do any harm (apoptosis). However, in cancer cells the signals telling them to undergo apoptosis can be overridden so that the damaged cell continues to divide, producing even more damaged cells.

There are multiple methods currently in use to treat cancer, but the three most common treatments are surgery, chemotherapy and radiotherapy. In surgery, the tumour is simply removed from the body however this only completely cures if the cancer is contained in one area and hasn’t spread. Surgery is often used in combination with other treatments such as chemotherapy to shrink the tumour before surgery (neo adjuvant treatment).

Chemotherapy is the use of drugs to treat cancer, usually by stopping cells from dividing. The drugs do this by either preventing DNA from replicating (which occurs in the time preceding mitosis) or by interrupting mitosis during the metaphase stage. Chemotherapy is most effective against rapidly dividing cells like cancer cells but it can also effect other cells which divide frequently such as hair-producing cells. This explains some of the side effects such as loss of hair that can occur during chemotherapy.

Radiation works by damaging the DNA in cells that are dividing using high-energy rays (normally x-rays). Seems confusing, doesn’t it, given that cancer itself occurs due to damage to DNA in the first place? Radiation is different because the way in which it damages the cells means that they can’t grow or divide anymore. That damage can generally be repaired in normal cells, but not always which is why there are unwanted side effects to radiotherapy, but cancer cells cannot fix themselves so they die over time.

So now that you are clued up on how cancer occurs and can be stopped, back to carbon-dating. Carbon dating is used to determine the age of organic matter by measuring the amount of carbon-14 that they contain, but here’s the burn- I’m not really talking about carbon dating. Sorry! Don’t leave just yet, because what these scientists did to find out when various stages of cancer progressed in a patient is still pretty interesting. The researchers used genetic analysis and mathematical models that’s normally used in evolutionary biology and applied it to cancer instead. In evolutionary biology, genetic data from current species can be used in combination with carbon-dated fossils of ancestral species to estimate when the current species- or species in between ‘now’ and ‘then’- arose throughout history. Now you can perhaps see why the carbon-dating link comes in.

These methods could only be applied, however, due to a needle tract tumour which occurred when a biopsy of the patient’s tumour was taken. What this means is that a sample of the cancer was taken using a needle and where that needle was removed, some of the cancer cells contaminated the needle track. These cancer cells grew into a metastatic tumour (tumour which has spread from the primary site of cancer to a different area) but because the scientists knew exactly when this tumour happened, the genetic data from these cancer cells could be analysed and compared etcetera etcetera so that a timeline of how the cancer had started and spread was made.

This timeline is useful because it could help with diagnosis and treatment, not only directly but also from what else the scientists found. The researchers discovered that the cancer spread faster during the first year, however after metastasis this progression slowed. What this suggests is that the degree of genetic instability may play a more important part in the deadliness of cancer  than the amount that the cancer has spread. This could be used to determine a patient’s prognosis more accurately, and could help doctors when evaluating how well a treatment might- or might not- work. Furthermore, tracking a cancer’s progression could enable doctors to better predict the cancer’s behaviour in the future thus influencing the strategy for treating it.

So that’s a bit of information about what cancer is, how it can be treated and a recent research development in the field. Some of what I have shared in this post, I learnt at a ‘medicine insight day’ hosted by a group of medical students at Oxford University. They shared with us tips on how to get into university, explained some of the science in cancer and educated us about ovarian and testicular cryopreservation- a method to preserve the fertility of teenagers who have survived cancer.

This preservation is necessary because if a young person survives cancer, the treatment against cancer is often so aggressive that an ‘early menopause’ is triggered in the patient meaning they become infertile (unable to have children). The Future Fertility Trust is  charitable trust fund which offers cryopreservation in which ovarian or testicular tissue is collected, stored and re-implanted after cancer treatment. This enables young cancer survivors to have children in later life, however the work is not funded by the NHS so relies on donations and fundraising. I would like to see ovarian and testicular cryopreservation help more young people and hope that it might become available to all young people by the NHS is the future, and this could be possible if enough cases are funded to show the usefulness and success of  the technique. If you would like to find out more about cryopreservation, Future Fertility Trust, or to donate, go to http://www.futurefertilitytrustuk.org.

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Does the 5-second rule really work?

I’m sure you’re familiar with and maybe even ‘daring’ enough to use the 5-second rule, but a news article this week has brought this question to my attention as Professor Anthony Hilton has decreed that it’s indeed true, to a degree. For those of you who actually don’t know what it is, the 5-second rule suggests that if food is dropped on the floor, it can still be eaten if it is picked up within a window of 5 seconds.

 

Notably since 2003, scientists have been making attempts to prove or disprove this theory with Jillian Clarke starting the proceedings by proving that foods will be contaminated- even with brief exposure- to a floor inoculated with E.coli. She did, however, also find that there was little evidence that public floors are in fact contaminated. In 2006, another study found that bacteria could thrive under dry conditions for over a month and that contamination does increase as the food is left on the floor for longer.

Researchers at Rutgers University tested extensively using different surfaces and foods with a total of 2,560 measurements to find that wet foods pick up more contaminants than dry, and that carpet is surprisingly a better surface than steel or tile when it comes to transference of bacteria. Lead researcher Professor Schaffner states, “Bacteria can contaminate instantaneously” and the evidence agrees, but does that answer the question?

As previously mentioned, Anthony Hilton at Aston University led a study in 2014 which found much the same as Schaffner’s yet suggests such results support the 5-second claim. Whilst he accepts that bacteria is inevitably picked up and that eating food from the floor is never “entirely risk-free”, he also points out that the research shows food is unlikely to pick up harmful bacteria from the few seconds spent on the floor. Furthermore, he has said there should be little concern about food that has touched the floor for such a short time. I think that this conclusion rings true with more of the general public than the latter, with 79% of 2000 people admitting to eating food that had fallen on the floor.

 

My view is that most people do not truly believe zero bacteria is picked up in those precious 5 seconds, but assume that the amount is negligible and neither numerous nor dangerous enough to cause any harm. The science does show that the longer food is on the floor, the more bacteria is picked up and in those first 5 seconds any harm from said bacteria is unlikely. Therefore, I would argue that the 5-second rule does work, but really it is up to personal preference and circumstance. But if you’ve dropped a slice of watermelon (made up of 97% water) on a visibly dirty tile, I’d say give it a miss- it’s just common sense…

 

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Technology & Medicine

Technology has integrated itself every aspect of life and medicine is no exception. From 3D printing of organs to genetic engineering of embryos, advances in technology directly link to advances in medicine and here’s just a couple examples of present and future applications of it…

 

Walking around a city centre, you probably don’t notice the AED machines that you may pass in train stations, shopping centres and leisure centres but from now on I implore you to take a notice, as you could save a life. Yes, you! The great thing about the automated external defibrillator is that it’s designed for non-medical people (laypersons) with simple audio and visual commands to guide the user through the appropriate steps to be taken- although it would ideally be used by someone who has received AED training.

It is used in cases of cardiac arrhythmia  (irregular heartbeat) leading to cardiac arrest. However, AEDs aren’t designed to shock asystolic patients (flatline) so it is very important that CPR is carried out before the AED is used, and during if you are instructed. An AED is ‘automated’ because of the unit’s ability to automatically diagnose the heart rhythm and determine if a shock is needed. Following a shock, most devices will analyse the patient and either instruct the user to give CPR or administer another shock. An AED is likely to have an ‘event memory’ also, which stores the ECG of the patient along with details of the number, strength and time of any shocks delivered. So keep a look out for any AED machines in public settings and should you ever be in a position where have to use one, be grateful that in that admittedly pressured environment the automated external defibrillator will do most of the legwork for you.

 

Virtual reality is an immersive simulation of a 3D environment, created by technology and experienced by movement of the body. It has been used in gaming for some time now, but has been branching out into many more sectors including usage in museums, education and military training as the technology for VR has advanced. And now, a team of Cardiff University psychologists are working to develop virtual reality environments to help with the diagnosis and rehabilitation of patients suffering from visual vertigo.

Symptoms of visual vertigo include dizziness and nausea, these can be sparked by various environments depending on the sufferer and can be so debilitating that in some cases a patient cannot even leave their house. It is very difficult to rehabilitate patients as it cannot be fixed quickly and patients have to be seen multiple times. By using VR, the team in Cardiff have flexibility over the different environments they can show to patients- this will allow them to find out a patient’s individual trigger and subsequently tailor specific rehabilitation therapies.

Immersive VR therapy could also be used to rehabilitate stroke and brain injury victims to help them regain motor and cognitive function faster. What’s more, the exercises could be made to feel like games to motivate patients to practice everyday. Whilst little in the way of virtual reality in medicine has been implemented yet, it does look very promising and I am keen to see further research into it…

 

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A Broken Heart- Can you die from one?

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It’s a romantic sentiment,  the idea that the death of a loved one or even a break up can ‘break’ your heart, but is it a real thing and could you actually die from one? Something I’d not considered until a news article a little while ago sparked my interest and got me researching, and here’s what I’ve found…

 

Broken heart syndrome, or in medical terms Takotsubo cardiomyopathy, is a type of non-ischemic cardiomyopathy (not caused by coronary artery disease) in which  the heart muscles are temporarily weakened as a result of emotional stress or physical stress, although in some cases even happier events trigger it such as winning a lot of money. Some drugs can also cause broken heart syndrome for example the epinephrine used to treat asthma attacks and allergic reactions.

The cause of broken heart syndrome is not exactly known, but it is thought to be linked to a surge in stress hormones like adrenaline which might temporarily damage the heart. How the hormones damage the heart is even less clear, the main idea being due to a temporary constriction of coronary arteries and another theory being that the hormones cause part of the heart to stop beating and another section of the heart to beat too fast or too hard.

 

So where does the name Takotsubo come from? Well, it comes from the Japanese word for an octopus trap because in Takotsubo cardiomyopathy, the left ventricle changes shape to develop a narrow neck and round bottom, thus resembling the fishing pot.

Other symptoms of Broken Heart Syndrome include chest pain, shortness of breath and ECG changes mimicking a heart attack. In some cases, people may also suffer collapsing, nausea and vomiting.

The symptoms might mimic a heart attack, but Takotsubo cardiomyopathy is clinically different in that the patients are at low risk of heart disease, are generally healthy prior to the triggering event and recovery rates are faster than with a normal heart attack. It can occur at any age, but in general affects post-menopausal women and those with past or present neurological or psychiatric disorders are at higher risk also.

So now we know that the ‘broken heart’ is a real thing…sort of… we can answer the real question; can you die from one? Most who experience Broken Heart Syndrome recover within two months, but in rare cases it can be fatal. There is a very low rate of complications like pulmonary edema (fluid in the lungs), hypotension (low blood pressure) or heart failure and unless there is an underlying heart problem, long term treatment or medication isn’t necessary.

As for dying from Takotsubo cardiomyopathy, there’s a  number of cases of elderly couples dying within weeks, days or even hours of each other and similar cases between mothers who lose children. However, given that only around 2% of ‘heart attacks’ are actually Takotsubo cardiomyopathy, the chances of then dying from it as opposed to the normal fast recovery is not exactly high. Of course it generally occurs in healthy patients, so there aren’t any preventative measures that can be taken except supporting grieving, anxious and stressed loved ones through tough (and sometimes successful) times.

The only thing left to say is that I think there’s something quite poetic about broken heart syndrome, a rather beautiful Shakespearian tragedy with a modern medical twist.

 

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