tag:theconversation.com,2011:/uk/topics/penicillin-30145/articlesPenicillin – The Conversation2024-01-29T14:53:48Ztag:theconversation.com,2011:article/2215112024-01-29T14:53:48Z2024-01-29T14:53:48ZFrom mud and vinegar to 3D printing skin, the way we treat wounds still challenges humanity<p>Whether it’s the sting of a paper cut or the trauma of battle injury, wounds are woven into the tapestry of human experience. And since ancient times, we’ve fought the enemy that lurks within them – infection. </p>
<p>The constant threat of injury on the battlefield led to the search for new ways to combat wound infection. But early surgical procedures lacked the sterile instruments available today, meaning that for many years, surgery came with the added risk of post-operative <a href="https://cha.com/wp-content/uploads/2017/11/AJIC-2012-Infection-Control-Through-the-Ages.pdf">wound infection</a>, resulting in high numbers of deaths. </p>
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3601883/">Ancient practices</a>, such as using oils, mud, turpentine, or honey to treat wounds, were common around 2000BC. The Greek physician Hippocrates (460-377BC) <a href="https://www.dermatologytimes.com/view/acetic-acid-and-wound-healing">used vinegar</a> to clean wounds, followed by bandaging to keep dirt at bay.</p>
<p>While the first hospitals were <a href="https://scientificsurgery.bjs.co.uk/article/the-surgery-of-theodoric-ca-a-d-1267-translated-from-the-latin-by-eldridge-campbell-m-d-and-james-colton-m-a-volume-i-books-i-and-ii-8-38-x-5-12-in-pp-223-xi-with-coloured-front/">established</a> in Europe in the middle ages, they were dangerous and brutal places. Wound infection rates were high because of unsanitary conditions and the use of cautery, which involved pushing a burning iron into a patient’s wound until it reached the bone.</p>
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<img alt="A drawing of a pot containing a fire with several medical instruments poking out of it." src="https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=403&fit=crop&dpr=1 600w, https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=403&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=403&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=506&fit=crop&dpr=1 754w, https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=506&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=506&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">A receptacle for burning coal to heat cautery instruments.</span>
<span class="attribution"><a class="source" href="https://wellcomecollection.org/works/gcg933n2/images?id=jghkdnp4">Wellcome Collection</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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<p>By the 1860s, the pioneering surgeon Joseph Lister had revolutionised wound infection treatment by introducing <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2895849/">carbolic-acid-soaked bandages</a>. And Robert Wood Johnson, who founded Johnson & Johnson, <a href="https://wounds-uk.com/journal-articles/sterilised-gauze-and-baby-powder-robert-wood-johnson-i-and-frederick-barnett-kilmer/">produced</a> the first sterile gauze bandages by 1890. The combination of antiseptic and sterile bandage marked a turning point in the evolution of wound treatment and infection control.</p>
<p>The discovery of penicillin by <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520913/">Alexander Fleming</a> in 1928 was also a pivotal moment in the treatment of wound infections. By the 1940s, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5369031/">penicillin</a> was being used to treat second world war soldiers who had wound infections that would have been deemed fatal in previous years. For less serious wounds, Lister’s approach of using a dressing and an antiseptic was still used.</p>
<p>Substances like <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756674/">silver</a> and <a href="https://pubmed.ncbi.nlm.nih.gov/12914356/">iodine</a> have also been recognised for their antimicrobial properties since the 1800s. Iodine, though effective, caused pain and skin discolouration until safer and less painful formulations were developed in 1949. <a href="https://bnf.nice.org.uk/wound-management/antimicrobial-dressings/">These formulations</a> endure in modern wound dressings.</p>
<p>For everyday cuts and scrapes, a simple cleaning with water and application of antiseptic cream is usually enough. This helps to prevent the inadvertent introduction of bacteria into the wound, minimising the risk of additional pain and swelling. </p>
<p>But while most wounds nowadays heal without issue, some become become infected. Research published in 2021 showed that <a href="https://wounds-uk.com/wp-content/uploads/sites/2/2023/02/68803cd147c4d81a02b9cc56823f19a1.pdf">3.8 million</a> people were having their wounds managed by the NHS between 2017 and 2018, up 71% from between 2012 and 2013. They included surgical wounds, leg ulcers and burns. This shows how hard it can be to care for wounds that are difficult to heal and particularly susceptible to infections.</p>
<h2>Modern-day challenges</h2>
<p>One of the biggest challenges in the modern-day treatment of wound infection is <a href="https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance">antibiotic resistance</a>. This happens when bacteria develop the ability to defeat the drugs designed to kill them. Resistant infections can be difficult, and sometimes impossible, to treat. </p>
<p>Many bacteria have also become resistant to the antimicrobial ingredients used in wound dressings. This is the case for <a href="https://www.sciencedirect.com/science/article/pii/S0195670104005201">silver-based</a> wound dressings, which are often used to treat chronic wound infections. This type of wound characteristically <a href="https://www.nature.com/articles/s41572-022-00377-3">fails to heal</a>, and can remain an open, infected wound for many months – or even years. As well as the devastating effect on people’s quality of life, this also places a huge financial burden on the NHS.</p>
<p>The constant fight against wound infections drives extensive research for new, safe and effective treatments. While progress is being made, a crucial hurdle lies in the <a href="https://academic.oup.com/jacamr/article/3/1/dlab027/6186407">limitations</a> of laboratory testing methods. These tests, while necessary for regulatory approval, often fail to capture the nuanced realities of wounds in the human body. </p>
<p>No two people are the same and no two wounds are the same either. This can lead to situations where treatments shine in the lab but ultimately prove ineffective in real patients.</p>
<h2>Creating wound models</h2>
<p>In response to this, scientists are tackling the limitations of lab tests by creating more realistic synthetic wound models. Some are even <a href="https://pubmed.ncbi.nlm.nih.gov/30172300/">3D printing</a> human skin (using leftovers from surgical procedures), or animal skin, complete with artificial body fluids, such as pus. The aim is to create a model environment that mimics real wounds more accurately. </p>
<p>Recently, my own <a href="https://pubmed.ncbi.nlm.nih.gov/36678466/">research group</a> has made strides in developing lab models that act like real chronic wounds when treated with antimicrobial dressings. While not perfect, our models are a step in the right direction, contributing to the development of formulations with promising potential for treating wound infections in the future.</p>
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Read more:
<a href="https://theconversation.com/we-built-a-human-skin-printer-from-lego-and-we-want-every-lab-to-use-our-blueprint-203170">We built a human-skin printer from Lego and we want every lab to use our blueprint</a>
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<p>As we navigate the complexities of wound care, the quest for new, effective and safe treatments continues, driven by the efforts of scientists worldwide. We are working towards a future where the management of difficult-to-heal wounds and infections improves, enhancing both individual wellbeing and the efficiency of health systems.</p><img src="https://counter.theconversation.com/content/221511/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sarah Maddocks does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Keeping wounds clean and infection free has challenged people for thousands of years.Sarah Maddocks, Lecturer in Microbiology, Cardiff Metropolitan UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2205642024-01-05T14:54:09Z2024-01-05T14:54:09ZNew antibiotic zosurabalpin shows promise against drug-resistant bacteria – an expert explains how it works<figure><img src="https://images.theconversation.com/files/567989/original/file-20240105-24-a6i28q.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C5120%2C2880&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Carbapenem-resistant Acinetobacter baumannii is classified as a priority 1 critical pathogen by the World Health Organization</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/medical-science-laboratory-portrait-beautiful-black-1922200124">Gorodenkoff/Shutterstock</a></span></figcaption></figure><p>Researchers have <a href="https://www.nature.com/articles/s41586-023-06799-7">identified</a> an entirely new class of antibiotic that can kill bacteria that are resistant to most current drugs. </p>
<p>Zosurabalpin is highly effective against the bacterium carbapenem-resistant <em>Acinetobacter baumannii</em> (Crab), which is <a href="https://www.who.int/news/item/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed">classified</a> as a “priority 1” pathogen by the World Health Organization due to its growing presence in hospitals.</p>
<p>Crab <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9137960/">can kill</a> up to 60% of people infected with it. It commonly causes infections of the urinary tract, respiratory tract and blood stream, potentially leading to sepsis. It is responsible for <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6913636/">around 20%</a> of infections in places like hospitals, care homes or other similar healthcare settings.</p>
<p>Antibiotics commonly work by crossing the cell wall that surrounds infectious bacteria to reach the vital machinery inside. Once inside the cell, antibiotics block that machinery in such a way as to either stop the bacteria from growing or to cause cell death. </p>
<p>Crab is a clinical challenge as it has a double-layered cell wall, a feature that microbiologists describe as “<a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/gram-negative-bacteria">gram negative</a>”. This means that antibiotics need to cross both layers to reach the vital machinery inside the bacteria to kill them and treat the infection. </p>
<p>An exception to this rule is penicillin-based antibiotics, where the target is in the cell wall itself. These antibiotics, known as <a href="https://www.bmj.com/content/344/bmj.e3236">carbapenems</a>, were derived from penicillin some 48 years after it was first discovered and still work in the same way. However, they have undergone clever chemical modification to prevent bacteria successfully evolving to resist them. This makes them a vital part of treating infections like those caused by <em>Acinetobacter baumannii</em>. </p>
<p>But Crab, the superbug version of this infection, has developed the ability to break down carbapenems, giving it an evolutionary upper hand, which has led to its rise to supremacy in hospitals. </p>
<h2>Zosurabalpin</h2>
<p>This new class of antibiotic, zosurabalpin, is shown to be highly effective against Crab both in the laboratory and in infected animals. Researchers tested zosurabalpin against more than 100 Crab samples from patients suffering from the infection. The research team, <a href="https://www.nature.com/articles/s41586-023-06799-7">found</a> that zosurabalpin was able to kill all of these bacterial strains. It could also kill the bacteria in the bloodstream of mice infected with Crab, preventing them from developing sepsis. </p>
<p>Crab has the ability to make a toxin called <a href="https://www.sciencedirect.com/topics/neuroscience/lipopolysaccharide">lipopolysaccharide</a> that it uses as part of its weaponry for infecting people and which it normally embeds into its outer cell wall. </p>
<p>Zosurabalpin works by blocking a molecular machine called <a href="https://www.nature.com/articles/s41586-023-06873-0">LptB2FGC</a> that transports the lipopolysaccharide toxin from the inside barrier to the outside one. This makes the toxin build up inside the bacteria, causing the Crab cells to die. Essentially, the bacteria pull the pin out of their own grenade but zosurabalpin stops them from being able to throw it. </p>
<p>This LptB2FGC mechanism is pretty unique to Crab, which has some advantages and disadvantages. The bad news is that zosurabalpin will only kill Crab infections and not those caused by other types of bacteria. This means doctors would need to accurately diagnose patients with this infection to decide if zosurabalpin would be the right drug. </p>
<p>But a major advantage is that the chance of antibiotic resistance emerging is reduced, as this resistance could only emerge from Crab and not other types of bacteria. Hopefully, this could extend the shelf life of this drug. </p>
<p>The researchers say they have already seen some mutations in the drug target, LptB2FGC. However, these only seem to reduce the effectiveness of zosurabalpin, rather than stopping it working entirely. The great news is that this is the first time an antibiotic has been reported to work in this way. It gives microbiologists a new avenue to explore ways to kill our bacterial enemies before they kill us. </p>
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<img alt="Close up of microscope with lab glassware." src="https://images.theconversation.com/files/568021/original/file-20240105-25-qzeyh5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/568021/original/file-20240105-25-qzeyh5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/568021/original/file-20240105-25-qzeyh5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/568021/original/file-20240105-25-qzeyh5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/568021/original/file-20240105-25-qzeyh5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/568021/original/file-20240105-25-qzeyh5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/568021/original/file-20240105-25-qzeyh5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Zosurabalpin is effective against the bacteria, Crab, which can kill up to 60% of people infected with it.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/microscope-lab-glassware-science-laboratory-research-530971462">totojang1977/Shutterstock</a></span>
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<p>Zosurabalpin is now in phase 1 clinical trial for use in patients infected with Crab. This early testing in humans will help the company developing the drug, Roche, to work out any side effects of the drugs as well as potential toxicity. Most importantly, they need to check that the drug works just as well in humans as it did in mice, and look to see if any antibiotic resistance emerges in the trial patients. </p>
<p>It’s early days and the failure rate for new antibiotic development is high, but scientists are rising to the challenge. This discovery offers significant opportunities to the scientific field as a whole and a vital lifeline in the fight against antibiotic-resistant infections.</p><img src="https://counter.theconversation.com/content/220564/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jonathan Cox receives research funding from UKRI, charities and industry.
He is Co-Director of the Antibiotic Discovery Accelerator (ABX) Network </span></em></p>Zosurabalpin is highly effective against dangerous bacterium Crab, which can kill up to 60% of people infected with it.Jonathan Cox, Senior Lecturer in Microbiology, Aston UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2128742023-11-08T19:10:33Z2023-11-08T19:10:33ZDo you think you have a penicillin allergy? You might be wrong<figure><img src="https://images.theconversation.com/files/555945/original/file-20231025-19-tbp1oy.jpg?ixlib=rb-1.1.0&rect=98%2C160%2C8144%2C5326&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/these-all-possible-causes-shot-young-2148946861">Shutterstock</a></span></figcaption></figure><p><em>Antimicrobial resistance is <a href="https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance">one of the biggest global threats</a> to health, food security and development. This month, The Conversation’s <a href="https://theconversation.com/au/topics/the-dangers-of-antibiotic-resistance-146983">experts explore how we got here and the potential solutions</a>.</em></p>
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<p>Penicillins are the most prescribed class of antibiotics in Australia. Originally derived from a fungus, penicillin antibiotics such as amoxicillin are used to treat common infections, including chest, sinus, ear, urinary tract and skin infections. </p>
<p>Penicillins are effective against a wide range of bacteria that cause common infections. But their activity is not so broad as to impact on good bacteria in our gut like other antibiotic classes do. They’re also cheap and readily accessible.</p>
<p>Up to <a href="https://www.sciencedirect.com/science/article/pii/S2772829322000376#bib1">20%</a> of Australians admitted in hospital say they have a penicillin allergy.</p>
<p>But not everyone who thinks they’re allergic to penicillin actually is. Research from <a href="https://www.sciencedirect.com/science/article/pii/S2772829322000376?via%3Dihub">our team</a> and others suggests that if we assess all these patients, up to 90% are not allergic to it.</p>
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Read more:
<a href="https://theconversation.com/weekly-dose-penicillin-the-mould-that-saves-millions-of-lives-63770">Weekly Dose: penicillin, the mould that saves millions of lives</a>
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<h2>Why does it matter?</h2>
<p>People who mistakenly think they’re allergic to penicillin may not get the most effective or safest antibiotics to treat their infection. </p>
<p>They are also at greater risk of developing <a href="https://www.sciencedirect.com/science/article/abs/pii/S009167491301467X">multidrug-resistant infections</a> or “superbugs”. This is because the antibiotic will kill off the bacteria that are susceptible to it, but the resistant bacteria are left behind to proliferate and cause further infection.</p>
<p>People who receive second-line antibiotics are more likely to have complications, such as <a href="https://www.sciencedirect.com/science/article/abs/pii/S009167491301467X">antibiotic-induced gut infections</a>. Second-line antibiotics tend to have a wider range of activity, killing both the bacteria causing infection, and the good bacteria required to keep our gut in balance. This allows bugs like <em>Clostridium difficile</em>, which normally lives in our gut but is controlled by other bacteria, to overgrow and cause inflammation. </p>
<p>For the health system, using second-line antibiotics means longer, more complicated hospital stays. Hospital stays for patients with penicillin allergies cost up to <a href="https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1365-2222.2003.01638.x">63% more</a> more than those without. It also results in greater costs for medications and greater resources required to treat the patient. </p>
<h2>Why do people think they’re allergic?</h2>
<p>People incorrectly believe they are allergic to penicillin for a number of reasons. </p>
<p>They may have experienced side effects from penicillin, such as nausea or diarrhoea. But though unpleasant, this doesn’t mean an allergy.</p>
<p>Others had a rash as a child, but this could have been due to the illness itself or an interaction between the virus and the antibiotic. An Epstein-Barr viral infection treated with amoxicillin, for example, <a href="https://pubmed.ncbi.nlm.nih.gov/23589810/">causes</a> a fine, red rash. </p>
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<img alt="Woman sits it wheelchair in hospital" src="https://images.theconversation.com/files/555944/original/file-20231025-23-83c11.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/555944/original/file-20231025-23-83c11.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/555944/original/file-20231025-23-83c11.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/555944/original/file-20231025-23-83c11.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/555944/original/file-20231025-23-83c11.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/555944/original/file-20231025-23-83c11.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/555944/original/file-20231025-23-83c11.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">It’s important to know your true allergy status when you go to hospital.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/rear-view-senior-asian-woman-sitting-1605865573">Shutterstock</a></span>
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<p>Some believe a family history of reactions to penicillin means they cannot take them. But there is no evidence penicillin allergy is inherited. </p>
<p>If some time has passed between exposure, people can lose the allergic response. This is typically seen in adults who had a mild allergy as a child, but lose the response with time, so are said to have “grown out” of their allergy.</p>
<p>Then there are people who have had a genuine and serious reaction to penicillin. This includes anaphylaxis, with profound swelling, breathing difficulties and low blood pressure, and severe life-threatening reactions such as <a href="https://www.ncbi.nlm.nih.gov/books/NBK459323/#:%7E:text=Stevens%2DJohnson%20syndrome%2Ftoxic%20epidermal,in%20over%2080%25%20of%20cases.">Steven-Johnson’s syndrome</a>, which causes widespread blisters and wounds that resemble burns.</p>
<h2>Testing for penicillin</h2>
<p>When someone says they have a penicillin allergy, we first get them to explain what happened with the reaction, including to what antibiotic, in what context and how severe it was. </p>
<p>Then we perform skin tests to further assess the person’s risk of reaction. If skin tests are negative, we can then give the patient the penicillin in question under supervision (a “challenge”) to see if they react. </p>
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<img alt="Allergist performs skin test on patient's arm" src="https://images.theconversation.com/files/555946/original/file-20231025-27-q72zcu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/555946/original/file-20231025-27-q72zcu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/555946/original/file-20231025-27-q72zcu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/555946/original/file-20231025-27-q72zcu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/555946/original/file-20231025-27-q72zcu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/555946/original/file-20231025-27-q72zcu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/555946/original/file-20231025-27-q72zcu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Skin tests assess a patient’s reaction to the allergen.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/allergy-skin-prick-tests-184605983">Shutterstock</a></span>
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<p>Some people can skip the skin tests altogether and go straight to the challenge if the history tells us they are at low risk of reacting.</p>
<p><a href="https://www.sciencedirect.com/science/article/pii/S2772829322000376?via%3Dihub">Our study</a> followed 195 patients who reported a penicillin allergy across six Sydney hospitals. In the first phase, we assessed 85 people and found 82% weren’t allergic to penicillin. </p>
<p>In the second phase, we assessed 110 people, of whom 69% weren’t allergic.
This is slightly lower than research on the population as a whole, because we only looked at people who were referred for an allergy assessment. Many more patients carry an allergy label than those referred for testing.</p>
<p>In our study, eight weeks after their test, just 54% of participants in phase one correctly knew their penicillin allergy status. Some allergic people believed they were not allergic, and many non-allergic people believed they were allergic.</p>
<p>For phase two, we ensured people received a standardised letter outlining their results in addition to having a doctor or nurse explain them. This time, 92% were correct in their understanding when contacted eight weeks later. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/will-we-still-have-antibiotics-in-50-years-we-asked-7-global-experts-214950">Will we still have antibiotics in 50 years? We asked 7 global experts</a>
</strong>
</em>
</p>
<hr>
<h2>Reducing long waits for allergy tests</h2>
<p>Ruling out allergies among people who think they can’t have penicillin is time- and labour-intensive. The wait time from someone first being referred to an allergy clinic to having testing can be <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10026071/">up to two years</a>. And it’s usually not available outside major metropolitan hospitals. </p>
<p>We need to improve access to testing and also look at <em>when</em> people can access allergy services. When a person is sick in hospital with a serious infection, it’s not the right time for testing.</p>
<p>We also need to ensure the results of allergy tests translate to the real world so people know their true allergy status. The fragmentation of our medical records are a barrier to clear and effective communication of a patient’s true allergy status, and urgently need to be improved.</p>
<hr>
<p><em>Read the other articles in The Conversation’s series on the dangers of antibiotic resistance <a href="https://theconversation.com/au/topics/the-dangers-of-antibiotic-resistance-146983">here</a>.</em></p><img src="https://counter.theconversation.com/content/212874/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Winnie Tong has received funding from Maridulu Budyari Gumal, the Sydney Partnership for Health, Education, Research and Enterprise (SPHERE), Triple I Clinical Academic Group seed grant 2017, and the Balnaves Foundation. The authors would like to acknowledge Professor Andrew Carr, their collaborators and participants on this project. </span></em></p><p class="fine-print"><em><span>Jacqueline Loprete does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Up to 20% of Australians admitted in hospital say they have a penicillin allergy. But not everyone who thinks they’re allergic to penicillin actually is.Winnie Tong, Clinical Immunologist & Allergist, Immunopathologist and Senior Lecturer, UNSW SydneyJacqueline Loprete, Postdoctoral fellow, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2134502023-11-07T19:35:17Z2023-11-07T19:35:17ZThe rise and fall of antibiotics. What would a post-antibiotic world look like?<figure><img src="https://images.theconversation.com/files/554665/original/file-20231019-25-r60wx5.jpg?ixlib=rb-1.1.0&rect=11%2C449%2C3982%2C2461&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://unsplash.com/photos/woman-in-blue-and-white-polo-shirt-standing-on-yellow-flower-field-during-daytime-CEFYNiM9xLk">Luke Jones/Unsplash</a></span></figcaption></figure><p><em>Antimicrobial resistance is <a href="https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance">one of the biggest global threats</a> to health, food security and development. This month, The Conversation’s experts <a href="https://theconversation.com/au/topics/the-dangers-of-antibiotic-resistance-146983">explore how we got here and the potential solutions</a>.</em></p>
<hr>
<p>These days, we don’t think much about being able to access a course of antibiotics to head off an infection. But that wasn’t always the case – antibiotics have been available for less than a century. </p>
<p>Before that, patients would die of relatively trivial infections that became more serious. Some serious infections, such as those involving the heart valves, were <a href="https://pubmed.ncbi.nlm.nih.gov/20173297/">inevitably</a> fatal. </p>
<p>Other serious infections, such as <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3070694/">tuberculosis</a>, weren’t always fatal. Up to a <a href="https://www.biorxiv.org/content/10.1101/729426v1.full.pdf">half</a> of people died within a year with the most severe forms, but some people recovered without treatment and the remainder had ongoing chronic infection that slowly ate away at the body over many years. </p>
<p>Once we had antibiotics, the outcomes for these infections were much better.</p>
<h2>Life (and death) before antibiotics</h2>
<p>You’ve probably heard of Alexander Fleming’s accidental <a href="https://www.acs.org/education/whatischemistry/landmarks/flemingpenicillin.html">discovery of penicillin</a>, when fungal spores landed on a plate with bacteria left over a long weekend in 1928. </p>
<p>But the <a href="https://www.ox.ac.uk/news/science-blog/penicillin-oxford-story">first patient</a> to receive penicillin was an instructive example of the impact of treatment.
In 1941, Constable Albert Alexander had a scratch on his face that had become infected. </p>
<p>He was hospitalised but despite various treatments, the infection progressed to involve his head. This required removing one of his eyes.</p>
<figure class="align-center ">
<img alt="Old hospital room" src="https://images.theconversation.com/files/554667/original/file-20231019-29-4a4qra.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/554667/original/file-20231019-29-4a4qra.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/554667/original/file-20231019-29-4a4qra.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/554667/original/file-20231019-29-4a4qra.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/554667/original/file-20231019-29-4a4qra.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/554667/original/file-20231019-29-4a4qra.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/554667/original/file-20231019-29-4a4qra.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">In 1941, Albert Alexander was hospitalised with a severe infection.</span>
<span class="attribution"><a class="source" href="https://www.pexels.com/photo/furniture-and-fixtures-in-a-hospital-room-13083355/">Jonathan Borba/Pexels</a></span>
</figcaption>
</figure>
<p>Howard Florey, the Australian pharmacologist then working in Oxford, was concerned penicillin could be toxic in humans. Therefore, he felt it was only ethical to give this new drug to a patient in a desperate condition. </p>
<p>Constable Alexander was given the available dose of penicillin. Within the first day, his condition had started to improve. </p>
<p>But back then, penicillin was difficult to produce. One way of extending the limited supply was to “recycle” penicillin that was excreted in the patient’s urine. Despite this, supplies ran out by the fifth day of Alexander’s treatment. </p>
<p>Without further treatment, the infection again took hold. Constable Alexander eventually died a month later.</p>
<p>We now face a world where we are potentially running out of antibiotics – not because of difficulties manufacturing them, but because they’re losing their effectiveness.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/will-we-still-have-antibiotics-in-50-years-we-asked-7-global-experts-214950">Will we still have antibiotics in 50 years? We asked 7 global experts</a>
</strong>
</em>
</p>
<hr>
<h2>What do we use antibiotics for?</h2>
<p>We currently use antibiotics in humans and animals for a variety of reasons. Antibiotics reduce the duration of illness and the chance of death from infection. They also prevent infections in people who are at high risk, such as patients undergoing surgery and those with weakened immune systems. </p>
<p>But antibiotics aren’t always used appropriately. <a href="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30084-0/fulltext">Studies</a> consistently show a dose or two will adequately prevent infections after surgery, but antibiotics are <a href="https://irp.cdn-website.com/d820f98f/files/uploaded/surgical-prophylaxis-prescribing-in-australian-hospitals-results-of-the-2020-surgical-national-antimicrobial-prescribing-survey.pdf">often</a> continued for several days unnecessarily. And sometimes we use the wrong type of antibiotic. </p>
<p><a href="https://irp.cdn-website.com/d820f98f/files/uploaded/antimicrobial-prescribing-practice-in-australian-hospitals-results-of-the-2020-hospital-national-antimicrobial-prescribing-survey.pdf">Surveys</a> have found 22% of antimicrobial use in hospitals is inappropriate. </p>
<figure class="align-center ">
<img alt="Pharmacist looks at label on medicine box" src="https://images.theconversation.com/files/554669/original/file-20231019-23-xes5p9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/554669/original/file-20231019-23-xes5p9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/554669/original/file-20231019-23-xes5p9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/554669/original/file-20231019-23-xes5p9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/554669/original/file-20231019-23-xes5p9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/554669/original/file-20231019-23-xes5p9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/554669/original/file-20231019-23-xes5p9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Antibiotics are used for longer than needed and sometimes the wrong type is used.</span>
<span class="attribution"><a class="source" href="https://unsplash.com/photos/woman-in-white-dress-shirt-and-black-pants-standing-near-brown-wooden-shelf-fTQHPb6r4wQ">National Cancer Institute/Unsplash</a></span>
</figcaption>
</figure>
<p>In some situations, this is understandable. Infections in different body sites are usually due to different types of bacteria. When the diagnosis isn’t certain, we often <a href="https://onlinelibrary.wiley.com/doi/full/10.1111/resp.13334">err</a> on the side of caution by giving broad spectrum antibiotics to make sure we have active treatments for all possible infections, until further information becomes available.</p>
<p>In other situations, there is a degree of inertia. If the patient is improving, doctors tend to simply continue the same treatment, rather than change to more appropriate choice. </p>
<p>In general practice, the issue of diagnostic uncertainty and therapeutic inertia are often magnified. Patients who recover after starting antibiotics don’t usually require tests or come back for review, so there is no easy way of knowing if the antibiotic was actually required. </p>
<p>Antibiotic prescribing can be more complex again if <a href="https://www.mja.com.au/journal/2014/201/2/antibiotic-prescribing-practice-residential-aged-care-facilities-health-care">patients</a> are expecting “a pill for every ill”. While doctors are generally good at educating patients when antibiotics are not likely to work (for example, for viral infections), without confirmatory tests there can always be a lingering doubt in the minds of both doctors and patients. Or sometimes the patient goes elsewhere to find a prescription. </p>
<p>For other infections, resistance can develop if treatments aren’t given for long enough. This is particularly the <a href="https://pubmed.ncbi.nlm.nih.gov/11971765/">case</a> for tuberculosis, caused by a slow growing bacterium that requires a particularly long course of antibiotics to cure. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/tuberculosis-isnt-just-a-historical-disease-heres-how-it-spreads-and-who-is-at-risk-215154">Tuberculosis isn't just a historical disease. Here's how it spreads and who is at risk</a>
</strong>
</em>
</p>
<hr>
<p>As in humans, antibiotics are also used to prevent and treat infections in animals. However, a proportion of antibiotics are used for growth promotion. In Australia, an <a href="https://www.mja.com.au/journal/2019/211/4/antibiotic-use-animals-and-humans-australia">estimated</a> 60% of antibiotics were used in animals between 2005-2010, despite growth-promotion being phased out.</p>
<h2>Why is overuse a problem?</h2>
<p>Bacteria become resistant to the effect of antibiotics through natural selection – those that survive exposure to antibiotics are the strains that have a mechanism to evade their effects. </p>
<p>For example, antibiotics are sometimes given to <a href="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(18)30279-2/fulltext">prevent</a> recurrent urinary tract infections, but a consequence, any infection that does <a href="https://academic.oup.com/cid/article/73/3/e782/6141409">develop</a> tends to be with resistant bacteria.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/rising-antibiotic-resistance-in-utis-could-cost-australia-1-6-billion-a-year-by-2030-heres-how-to-curb-it-149543">Rising antibiotic resistance in UTIs could cost Australia $1.6 billion a year by 2030. Here's how to curb it</a>
</strong>
</em>
</p>
<hr>
<p>When resistance to the commonly used first-line antibiotics occurs, we often need to reach deeper into the bag to find other effective treatments. </p>
<p>Some of these last-line antibiotics are those that had been <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4202707/">superseded</a> because they had serious side effects or couldn’t be given conveniently as tablets. </p>
<p>New drugs for some bacteria have been developed, but many are much more <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955006/">expensive</a> than older ones. </p>
<h2>Treating antibiotics as a valuable resource</h2>
<p>The concept of antibiotics as a valuable resource has led to the <a href="https://pubmed.ncbi.nlm.nih.gov/8856755/">concept</a> of “antimicrobial stewardship”, with programs to promote the responsible use of antibiotics. It’s a similar concept to environmental stewardship to prevent climate change and environmental degradation. </p>
<p>Antibiotics are a rare class of medication where treatment of one patient can potentially affect the outcome of other patients, through the transmission of antibiotic resistant bacteria. Therefore, like efforts to combat climate change, antibiotic stewardship relies on changing individual actions to benefit the broader community.</p>
<figure class="align-center ">
<img alt="Surgeon ties her mask" src="https://images.theconversation.com/files/554670/original/file-20231019-27-9skfki.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/554670/original/file-20231019-27-9skfki.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/554670/original/file-20231019-27-9skfki.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/554670/original/file-20231019-27-9skfki.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/554670/original/file-20231019-27-9skfki.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/554670/original/file-20231019-27-9skfki.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/554670/original/file-20231019-27-9skfki.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Antimicrobial stewardship relies on individuals making decisions for the greater good.</span>
<span class="attribution"><a class="source" href="https://unsplash.com/photos/woman-in-teal-shirt-wearing-white-mask-8hHxO3iYuU0">SJ Objio/Unsplash</a></span>
</figcaption>
</figure>
<p>Like climate change, antibiotic resistance is a complex problem when seen in a broader context. Studies have linked resistance to the values and priorities <a href="https://www.thelancet.com/journals/lanplh/article/PIIS2542-5196(18)30186-4/fulltext">of governments</a> such as corruption and infrastructure, including the availability of electricity and public services. This highlights that there are broader “causes of the causes”, such as public spending on sanitation and health care. </p>
<p>Other <a href="https://academic.oup.com/jac/article/74/9/2803/5512029?login=true">studies</a> have suggested individuals need to be considered within the broader social and institutional influences on prescribing behaviour. Like all human behaviour, antibiotic prescribing is complicated, and factors like what doctors feel is “normal” prescribing, whether junior staff feel they can challenge senior doctors, and even their <a href="https://www.nytimes.com/2016/10/07/upshot/your-surgeon-is-probably-a-republican-your-psychiatrist-probably-a-democrat.html">political views</a> may be important. </p>
<p>There are also issues with the <a href="https://www.cambridge.org/core/journals/international-journal-of-technology-assessment-in-health-care/article/value-assessment-of-antimicrobials-and-the-implications-for-development-access-and-funding-of-effective-treatments-australian-stakeholder-perspective/D45758CFB95520DA4FF06E46135E0628">economic model</a> for developing new antibiotics. When a new antibiotic is first approved for use, the first reaction for prescribers is not to use it, whether to ensure it retains its effectiveness or because it is often very expensive. </p>
<p>However, this doesn’t really <a href="https://academic.oup.com/cid/article/50/8/1081/449089?login=true">encourage</a> the development of new antibiotics, particularly when pharma research and development budgets can easily be diverted to developing drugs for conditions patients take for years, rather than a few days. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/we-need-to-change-how-antibiotics-target-bugs-if-we-want-them-to-keep-working-183135">We need to change how antibiotics target bugs if we want them to keep working</a>
</strong>
</em>
</p>
<hr>
<h2>The slow moving pandemic of resistance</h2>
<blockquote>
<p>If we fail to act, we are looking at an almost unthinkable scenario where antibiotics no longer work and we are cast back into the dark ages of medicine
– <a href="https://amr-review.org/">David Cameron</a>, former UK Prime Minister </p>
</blockquote>
<p>Antibiotic resistance is already a problem. Almost all infectious diseases physicians have had the dreaded call about patients with infections that were essentially untreatable, or where they had to scramble to find supplies of long-forgotten last-line antibiotics. </p>
<p>There are already hospitals in some parts of the world that have had to carefully <a href="https://www.reactgroup.org/news-and-views/news-and-opinions/year-2022/the-impact-of-antibiotic-resistance-on-cancer-treatment-especially-in-low-and-middle-income-countries-and-the-way-forward/">consider</a> whether it’s still viable to treat cancers, because of the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276316/">high risk</a> of infections with antibiotic-resistant bacteria. </p>
<p>A global <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02724-0/fulltext">study</a> estimated that in 2019, almost 5 million deaths occurred with an infection involving antibiotic-resistant bacteria. Some 1.3 million would not have occurred if the bacteria were not resistant. </p>
<p>The UK’s 2014 <a href="https://amr-review.org/sites/default/files/AMR%20Review%20Paper%20-%20Tackling%20a%20crisis%20for%20the%20health%20and%20wealth%20of%20nations_1.pdf">O'Neill report</a> predicted deaths from antimicrobial resistance could rise to 10 million deaths each year, and cost 2-3.5% of global GDP, by 2050 based on trends at that time. </p>
<h2>What can we do about it?</h2>
<p>There is a lot we can do to prevent antibiotic resistance. We can:</p>
<ul>
<li><p><a href="https://www.marketingmag.com.au/news/film-picking-gonorrhoea-wins-tropfest-prize/">raise</a> <a href="https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-019-7258-3">awareness</a> that many infections will get better by themselves, and don’t necessarily need antibiotics </p></li>
<li><p>use the antibiotics we have more appropriately and for as short a time as possible, supported by co-ordinated clinical and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437704/">public policy</a>, and <a href="https://www.amr.gov.au/">national</a> <a href="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(22)00796-4/fulltext">oversight</a> </p></li>
<li><p><a href="https://www.safetyandquality.gov.au/our-work/antimicrobial-resistance/antimicrobial-use-and-resistance-australia-surveillance-system/about-aura-surveillance-system">monitor</a> for infections due to resistant bacterial to inform control policies </p></li>
<li><p>reduce the inappropriate use of antibiotics in animals, such as <a href="https://nam.edu/antibiotic-resistance-in-humans-and-animals/">growth promotion</a> </p></li>
<li><p><a href="https://pubmed.ncbi.nlm.nih.gov/11971765/">reduce</a> cross-transmission of resistant organisms in hospitals and in the community </p></li>
<li><p>prevent infections by other means, such as clean water, <a href="https://apps.who.int/iris/bitstream/handle/10665/204948/WHO_FWC_WSH_14.7_eng.pdf">sanitation</a>, hygiene and <a href="https://www.who.int/teams/immunization-vaccines-and-biologicals/product-and-delivery-research/anti-microbial-resistance">vaccines</a> </p></li>
<li><p>continue developing new antibiotics and alternatives to antibiotics and ensure the right <a href="https://www.thelancet.com/journals/lanepe/article/PIIS2666-7762(23)00124-2/fulltext#:%7E:text=We%20consider%20four%20incentive%20options,exclusivity%20extensions%2C%20and%20milestone%20payments.">incentives</a> are in place to encourage a continuous pipeline of new drugs.</p></li>
</ul>
<hr>
<p><em>Read the other articles in The Conversation’s series on the dangers of antibiotic resistance <a href="https://theconversation.com/au/topics/the-dangers-of-antibiotic-resistance-146983">here</a>.</em></p><img src="https://counter.theconversation.com/content/213450/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Allen Cheng receives funding from the Australian Government and the National Health and Medical Research Council. He is affiliated with the Centre to Impact Antimicrobial Resistance at Monash University. </span></em></p>Antibiotics have been around for less than a century. But as resistant bacteria become increasingly difficult to treat, we risk a greater number of deaths from infections.Allen Cheng, Professor of Infectious Diseases, Monash UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2113022023-10-17T16:42:46Z2023-10-17T16:42:46ZOnly 1% of chemical compounds have been discovered – here’s how we search for others that could change the world<figure><img src="https://images.theconversation.com/files/553049/original/file-20231010-21-ljmz9o.jpg?ixlib=rb-1.1.0&rect=49%2C74%2C5450%2C3586&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/chemical-tube-reaction-formula-light-598653854">Garsya/Shutterstock</a></span></figcaption></figure><p>The universe is flooded with billions of chemicals, each a tiny pinprick of potential. And we’ve only identified <a href="https://www.eurekalert.org/news-releases/993593">1% of them</a>. Scientists believe undiscovered chemical compounds could <a href="https://www.sciencedaily.com/releases/2021/08/210813100255.htm">help remove greenhouse gases</a>, or trigger a medical breakthrough much like penicillin did. </p>
<p>But let’s just get this out there first: it’s not that chemists aren’t curious. Since Russian chemist <a href="https://www.britannica.com/biography/Dmitri-Mendeleev">Dmitri Mendeleev</a> invented the <a href="https://www.britannica.com/science/periodic-table">periodic table of elements</a> in 1869, which is basically a chemist’s box of Lego, scientists have been discovering the chemicals that helped define the modern world. We needed nuclear fusion (firing atoms at each other at the speed of light) to make the last handful of elements. Element 117, <a href="https://www.rsc.org/periodic-table/element/117/tennessine">tennessine</a>, was synthesised in 2010 in this way. </p>
<p>But to understand the full scale of the chemical universe, you need to understand <a href="https://www.britannica.com/science/chemical-compound">chemical compounds</a> too. Some occur naturally – water, of course, is made of hydrogen and oxygen. Others, such as <a href="https://www.britannica.com/science/nylon">nylon</a>, were discovered in lab experiments and are manufactured in factories. </p>
<p><a href="https://www.bbc.co.uk/bitesize/topics/zstp34j/articles/zc86m39#:%7E:text=An%20element%20is%20a%20pure,There%20are%20118%20different%20elements.">Elements are made of one type of atom</a>, and <a href="https://www.livescience.com/37206-atom-definition.html">atoms are made of even tinier particles</a> including electrons and protons. All chemical compounds are made of two or more atoms. Although it’s possible there are undiscovered elements left to find, <a href="https://www.chemistryworld.com/news/beyond-element-118-the-next-row-of-the-periodic-table/9400.article">it’s unlikely</a>. So, how many <a href="https://www.wordnik.com/words/chemical%20compound">chemical compounds</a> can we make with the 118 different sorts of element Lego blocks we currently know?</p>
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<h2>Big numbers</h2>
<p>We can start by making all the <a href="https://www.britannica.com/science/diatomic-molecule">two-atom compounds</a>. There are lots of these: N<sub>2</sub> (nitrogen) and O<sub>2</sub> (oxygen) together make up 99% of our air. It would probably take a chemist about a year to make one compound and there are 6,903 two-atom compounds in theory. So that’s a village of chemists working a year just to make every possible two-atom compound. </p>
<p>There about 1.6 million three-atom compounds like H₂0 (water) and C0₂ (carbon dioxide), which is the population of Birmingham and Edinburgh combined. Once we reach four- and five-atom compounds, we would need everyone on Earth to make three compounds each. And to make <a href="https://sciencenotes.org/how-many-atoms-are-in-the-world/">all these chemical compounds</a>, we’d also need to recycle all the materials in the universe several times over. </p>
<p>But this is a simplification, of course. Things such as the structure of a compound and its stability can make it more complex and difficult to make.</p>
<p>The biggest chemical compound that has been made so far was <a href="https://pubs.acs.org/doi/full/10.1021/om900079y">made in 2009</a> and has nearly 3 million atoms. We’re not sure what it does yet, but <a href="https://doi.org/10.1039/C9TB02289A">similar compounds</a> are used to protect cancer drugs in the body until they get to the right place.</p>
<p>But wait, chemistry has rules! </p>
<h2>Surely not all those compounds are possible?</h2>
<p>It’s true there are rules – but they are kind of bendy, which creates more possibilities for chemical compounds. </p>
<p>Even the solitary “<a href="https://en.wikipedia.org/wiki/Noble_gas">noble gases</a>” (including neon, argon and xenon and helium), which tend to not bind with anything, <a href="https://www.aanda.org/articles/aa/abs/2014/06/aa23727-14/aa23727-14.html">sometimes form compounds</a>. Argon hydride, ArH<sup>+</sup> does not exist naturally on Earth but has been found in space. Scientists have been able to make synthetic versions in laboratories that replicate deep space conditions. So, if you include extreme environments in your calculations, the number of possible compounds increases. </p>
<p>Carbon normally likes being attached to between one and four other atoms, but very occasionally, for short periods of time, <a href="https://en.wikipedia.org/wiki/Methanium">five is possible</a>. Imagine a bus with a maximum capacity of four. The bus is at the stop, and people are getting on and off; while people are moving, briefly, you can have more than four people actually on the bus.</p>
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<em>
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Read more:
<a href="https://theconversation.com/confessions-of-a-chemist-i-make-molecules-that-shouldnt-exist-53326">Confessions of a chemist: I make molecules that shouldn't exist</a>
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<p>Some chemists spend their entire careers trying to make compounds that, according to the chemistry rulebook, shouldn’t exist. Sometimes they are successful.</p>
<p>Another question scientists have to grapple with is whether the compound they want can only exist in space or extreme environments – think of the immense heat and pressure found at <a href="https://oceanservice.noaa.gov/facts/vents.html">hydrothermal vents</a>, which are like geysers but on the ocean floor. </p>
<h2>How scientists search for new compounds</h2>
<p>Often the answer is to search for compounds that are related to ones that are already known. There are two main ways to do this. One is taking a known compound and changing it a bit – by adding, deleting or swapping some atoms. Another is taking a known chemical reaction and using new starting materials. This is when the method of creation is the same but the products may be quite different. Both of these methods are ways of searching for <em>known unknowns</em>. </p>
<p>Coming back to Lego, it’s like making a house, then a slightly different house, or buying new bricks and adding a second storey. A lot of chemists <a href="https://en.wikipedia.org/wiki/Mary_Elliott_Hill">spend their careers</a> exploring one of these chemical houses.</p>
<p>But how would we search for truly new chemistry – that is, <em>unknown unknowns</em>? </p>
<p>One way chemists learn about new compounds is to look at the natural world. Penicillin was found this way in 1928, when Alexander Fleming observed that mould in his petri dishes <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520913/">prevented the growth of bacteria</a>.</p>
<p>Over a decade later, in 1939, <a href="https://www.nobelprize.org/prizes/medicine/1945/florey/biographical/">Howard Florey</a> worked out how to grow penicillin in useful amounts, still using mould. But it took even longer, until 1945, for <a href="https://www.nobelprize.org/prizes/chemistry/1964/hodgkin/biographical/">Dorothy Crowfoot Hodgkin</a> to identify penicillin’s chemical structure. </p>
<p>That’s important because part of penicillin’s structure contains atoms arranged in a square, which is an unusual chemical arrangement that few chemists would guess, and is difficult to make. Understanding penicillin’s structure meant we knew what it looked like and could search for its chemical cousins. If you’re allergic to penicillin and have needed an alternative antibiotic, you have Crowfoot Hodgkin to thank. </p>
<p>Nowadays, it’s a lot easier to determine the structure of new compounds. The X-ray technique that Crowfoot Hodgkin invented on her way to identifying penicillin’s structure is still used worldwide to study compounds. And the same MRI technique that hospitals use to diagnose disease can <a href="https://www.acs.org/education/whatischemistry/landmarks/mri.html">also be used on chemical compounds</a> to work out their structure.</p>
<p>But even if a chemist guessed a completely new structure unrelated to any compound known on Earth, they’d still have to make it, which is the hard part. Figuring out that a chemical compound could exist does not tell you how it’s structured or what conditions you need to make it.</p>
<p>For many useful compounds, like <a href="https://www.nature.com/articles/ja2012126">penicillin</a>, it’s easier and cheaper to “grow” and extract them from moulds, plants or insects. Thus the scientists searching for new chemistry still often look for inspiration in the tiniest corners of the world around us.</p><img src="https://counter.theconversation.com/content/211302/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Matthew Addicoat receives funding from EPSRC and the Royal Society. </span></em></p>The limitless world of chemistry and how researchers investigate it.Matthew Addicoat, Senior Lecturer in Functional Materials, Nottingham Trent UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2146712023-10-04T14:15:47Z2023-10-04T14:15:47ZMost people who think they are allergic to penicillin aren’t<figure><img src="https://images.theconversation.com/files/552043/original/file-20231004-17-iavmz9.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C5190%2C3602&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/boston-massachusetts-united-states-december-2-1581332569">Michael Moloney/Shutterstock</a></span></figcaption></figure><p>About <a href="https://www.rpharms.com/about-us/news/details/millions-mistakenly-think-they-are-allergic-to-penicillin-#:%7E:text=Around%206%25%20of%20people%20have,to%20it%20when%20fully%20assessed.">6% of people in the UK</a> are wrongly labelled on their medical records as being allergic to penicillin, the Royal Pharmaceutical Society has warned.</p>
<p>This figure is concerning because being labelled as allergic to this class of highly effective antibiotics is associated with an extra <a href="https://academic.oup.com/jac/article/74/7/2075/5443267">six deaths per 1,000 patients</a> a year after being treated for an infection. If patients received the right antibiotic for their infection, many lives could be saved.</p>
<p>Allergies vary between us, but someone allergic to penicillin typically develops a rash, itching and swelling. Their throat may become tight and breathing difficult.</p>
<p>Diagnosing a penicillin allergy in an unwell person can be tricky. Typically, it is made when using penicillin to treat a feverish child with signs of an infected ear or throat. If they develop a rash, to be safe, the doctor may note on their medical records that they are allergic to the antibiotics. </p>
<p>This is done because someone allergic to penicillin typically responds badly to the next dose of penicillin, which can include the potentially lethal condition known as <a href="https://www.nhs.uk/conditions/anaphylaxis/">anaphylaxis</a>.</p>
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<p>This precautionary and often spurious label of “penicillin allergy” is highly likely to follow people through childhood and into their various medical records, without review and checking. These people continue to avoid penicillin treatments. So a great deal hinges on that rash.</p>
<p>However, rashes in people with a fever have many possible causes. A host of enteroviruses, to take one group of germs, give rise to rashes during an illness. And the Epstein-Barr virus will <a href="https://pubmed.ncbi.nlm.nih.gov/32346863/">often cause a rash</a> if a patient is treated with amoxicillin (an antibiotic from the penicillin family). And not all penicillin-induced rashes are allergic – they are just side-effects of the medicine. </p>
<p>Other symptoms such as diarrhoea or vomiting that might develop during a course of penicillin may represent an adverse reaction to the antibiotic, but not an allergy with any risk of future anaphylaxis. Some studies suggest that patients who once suffered an actual allergic reaction to penicillin may <a href="https://pubmed.ncbi.nlm.nih.gov/36916097/">lose this reaction over time</a>, so it is unclear if penicillin allergy is for life. </p>
<p>Those with “penicillin allergy” on their medical records have <a href="https://pubmed.ncbi.nlm.nih.gov/37666558/">worse health outcomes</a> and increased rates of <a href="https://pubmed.ncbi.nlm.nih.gov/30644987/">antimicrobial resistance</a> when treated with alternative, broad-spectrum antibiotics (broad-spectrum antibiotics kill a wide range of bacteria, not just the one suspected of causing infection).</p>
<p>Doctors <a href="https://pubmed.ncbi.nlm.nih.gov/36948494/">reporting from Pennsylvania in the US</a> this summer compared over 3,700 children and adolescents with pneumonia who had a penicillin allergy label with a similar number of those without. Those with the label had higher rates of hospitalisation, respiratory failure, intensive care treatment, adverse drug reactions and infection with <em>Clostridium difficile</em> (a type of bacteria that can cause a bowel infection). </p>
<p>Other studies have noted <a href="https://pubmed.ncbi.nlm.nih.gov/37153141/">increased risks of infections</a> following surgery, readmission to hospital, and <a href="https://pubmed.ncbi.nlm.nih.gov/33849960/">infection with the MRSA superbug</a> in “penicillin allergy” patients. These consequences are costly to patients, their families and health services. </p>
<h2>Find out if you are allergic</h2>
<p>A penicillin allergy can be confirmed by collecting exact information about how this developed, and sometimes skin prick tests or taking a very small dose of penicillin by mouth if required. GPs, nurses and pharmacists are being tasked to check drug allergy labels in medical records. Large surveys show these methods allow almost everyone to take this family of antibiotics safely.</p>
<p>Penicillins are routinely used as part of the treatment <a href="https://pubmed.ncbi.nlm.nih.gov/37110283/">in people with sickle cell anaemia</a>. They take the antibiotic twice a day, for life. Sickle cell anaemia is a common genetic condition. Over 12,000 people are followed regularly in the UK, yet <a href="https://pubmed.ncbi.nlm.nih.gov/11849580/">penicillin allergy in this group is rare</a>. This should provide reassurance about penicillin safety, placing allergies into a more reasonable perspective.</p>
<p>Accurate, up-to-date information is needed to support your health and that of others. If you think you have a penicillin allergy it would be wise to discuss and confirm this with your doctor. Removing this label might be of great benefit to you and others.</p><img src="https://counter.theconversation.com/content/214671/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Colin Michie does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Around 90% of people who have been incorrectly told by their doctor that they are allergic to penicillin.Colin Michie, Deputy Lead, School of Medicine, University of Central LancashireLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2020842023-05-08T12:18:30Z2023-05-08T12:18:30ZGain-of-function research is more than just tweaking risky viruses – it’s a routine and essential tool in all biology research<figure><img src="https://images.theconversation.com/files/523909/original/file-20230502-4095-u8oni1.jpg?ixlib=rb-1.1.0&rect=0%2C94%2C1500%2C1221&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Gain-of-function experiments in the lab can help researchers get ahead of viruses naturally gaining the ability to infect people in the wild.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/molecule-illustration-royalty-free-illustration/1423893041">KTSDesign/Science Photo Library via Getty Images</a></span></figcaption></figure><p>The term “gain of function” is often taken to refer to research with viruses that puts society at risk of an infectious disease outbreak for questionable gain. Some research on emerging viruses can result in variants that gain the ability to infect people but this does not necessarily mean the research is dangerous or that it is not fruitful. Concerns have focused on lab research on the <a href="https://www.theguardian.com/world/2012/mar/28/bird-flu-mutant-strains">virus that causes bird flu</a> in 2012 and on the <a href="https://theconversation.com/why-gain-of-function-research-matters-162493">virus that causes COVID-19</a> since 2020. The National Institutes of Health had previously implemented a <a href="https://www.science.org/content/article/nih-lifts-3-year-ban-funding-risky-virus-studies">three-year moratorium</a> on gain-of-function research on certain viruses, and some U.S. legislatures have <a href="https://www.washingtonexaminer.com/news/senate/texas-state-ban-gain-function-research-covid-pandemic">proposed bills prohibiting</a> gain-of-function research on “potentially pandemic pathogens.”</p>
<p>The possibility that a genetically modified virus could escape the lab needs to be taken seriously. But it does not mean that gain-of-function experiments are inherently risky or the purview of mad scientists. In fact, gain-of-function approaches are a fundamental tool in biology used to study much more than just viruses, contributing to many, if not most, modern discoveries in the field, including <a href="https://doi.org/10.3201%2Feid2305.161556">penicillin</a>, <a href="https://theconversation.com/anti-cancer-car-t-therapy-reengineers-t-cells-to-kill-tumors-and-researchers-are-expanding-the-limited-types-of-cancer-it-can-target-196471">cancer immunotherapies</a> and <a href="https://www.sciencedaily.com/releases/2015/02/150204134119.htm">drought-resistant crops</a>.</p>
<p>As <a href="https://scholar.google.com/citations?user=IXDoiY4AAAAJ&hl=en">scientists who</a> <a href="https://scholar.google.com/citations?user=GBQiazwAAAAJ&hl=en">study viruses</a>, we believe that misunderstanding the term “gain of function” as something nefarious comes at the cost of progress in human health, ecological sustainability and technological advancement. Clarifying what gain-of-function research really is can help clarify why it is an essential scientific tool.</p>
<h2>What is gain of function?</h2>
<p>To study how a living thing operates, scientists can change a specific part of it and then observe the effects. These changes sometimes result in the organism’s gaining a function it didn’t have before or losing a function it once had. </p>
<p>For example, if the goal is to enhance the tumor-killing ability of immune cells, researchers can take a sample of a person’s immune cells and modify them to express a protein that specifically targets cancer cells. This mutated immune cell, called a <a href="https://theconversation.com/anti-cancer-car-t-therapy-reengineers-t-cells-to-kill-tumors-and-researchers-are-expanding-the-limited-types-of-cancer-it-can-target-196471">CAR-T cell</a> thereby “gains the function” of being able to bind to cancerous cells and kill them. The advance of similar immunotherapies that help the immune system attack cancer cells is based on the exploratory research of scientists who synthesized such “<a href="https://doi.org/10.1007/BF00820662">Frankenstein” proteins</a> in the 1980s. At that time, there was no way to know how useful these chimeric proteins would be to cancer treatment today, some 40 years later. </p>
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<figcaption><span class="caption">CAR-T cell therapy involves giving a patient’s immune cells an increased ability to target cancer cells.</span></figcaption>
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<p>Similarly, by adding specific genes into rice, corn or wheat plants that increase their production in diverse climates, scientists have been able to produce plants that are able to grow and thrive in geographical regions they previously could not. This is a critical advance to maintain food supplies in the face of climate change. Well-known examples of food sources that have their origins in gain-of-function research <a href="https://www.sciencenews.org/article/rice-agriculture-feeds-world-climate-change-drought-flood-risk">include rice plants</a> that can grow in high flood plains or in drought conditions or that contain vitamin A to reduce malnutrition.</p>
<h2>Medical advances from gain-of-function research</h2>
<p>Gain-of-function experiments are ingrained in the scientific process. In many instances, the benefits that stem from gain-of-function experiments are not immediately clear. Only decades later does the research bring a new treatment to the clinic or a new technology within reach. </p>
<p>The development of most antibiotics have relied on the <a href="https://doi.org/10.3389/fcimb.2021.684515">manipulation of bacteria or mold</a> in gain-of-function experiments. Alexander Fleming’s initial discovery that the mold <em>Penicillium rubens</em> could produce a compound toxic to bacteria was a profound medical advance. But it wasn’t until scientists experimented with <a href="https://www.sciencemuseum.org.uk/objects-and-stories/how-was-penicillin-developed">growth conditions and mold strains</a> that therapeutic use of penicillin became feasible. Using a specific growth medium allowed the mold to gain the function of increased penicillin production, which was essential for its mass production and widespread use as a drug. </p>
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<a href="https://images.theconversation.com/files/523678/original/file-20230501-1518-hmu9o0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Worker monitoring penicillin capsules coming down production line" src="https://images.theconversation.com/files/523678/original/file-20230501-1518-hmu9o0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/523678/original/file-20230501-1518-hmu9o0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=759&fit=crop&dpr=1 600w, https://images.theconversation.com/files/523678/original/file-20230501-1518-hmu9o0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=759&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/523678/original/file-20230501-1518-hmu9o0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=759&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/523678/original/file-20230501-1518-hmu9o0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=954&fit=crop&dpr=1 754w, https://images.theconversation.com/files/523678/original/file-20230501-1518-hmu9o0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=954&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/523678/original/file-20230501-1518-hmu9o0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=954&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Gain-of-function research played a key role in the development and mass production of penicillin.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/penicillin-capsules-being-checked-as-they-come-off-the-news-photo/2667016">Wesley/Stringer/Hulton Archive via Getty Images</a></span>
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<p>Research on <a href="https://doi.org/10.1128%2FAAC.02381-18">antibiotic resistance</a> also relies heavily on gain-of-function approaches. Studying how bacteria <a href="https://theconversation.com/looming-behind-antibiotic-resistance-is-another-bacterial-threat-antibiotic-tolerance-200226">gain resistance</a> against drugs is essential to developing new treatments microbes are unable to evade quickly.</p>
<p>Gain-of-function research in virology has also been critical to the advancement of science and health. <a href="https://www.cancer.gov/news-events/cancer-currents-blog/2018/oncolytic-viruses-to-treat-cancer">Oncolytic viruses</a> are genetically modified in the laboratory to infect and kill cancerous cells like melanoma. Similarly, the <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/overview-COVID-19-vaccines.html">Johnson & Johnson COVID-19 vaccine</a> contains an adenovirus altered to produce the spike protein that helps the COVID-19 virus infect cells. Scientists developed <a href="https://onlinelibrary.wiley.com/doi/10.1002/(SICI)1099-1654(199910/12)9:4%3C237::AID-RMV252%3E3.0.CO;2-G">live attenuated flu vaccines</a> by adapting them to grow at low temperatures and thereby lose the ability to grow at human lung temperatures. </p>
<p>By giving viruses new functions, scientists were able to develop new tools to treat and prevent disease.</p>
<h2>Nature’s gain-of-function experiments</h2>
<p>Gain-of-function approaches are needed to advance understanding of viruses in part because these processes already occur in nature.</p>
<p>Many viruses that infect such nonhuman animals as bats, pigs, birds and mice have the potential to <a href="https://theconversation.com/what-is-spillover-bird-flu-outbreak-underscores-need-for-early-detection-to-prevent-the-next-big-pandemic-200494">spill over into people</a>. Every time a virus copies its genome, it makes mistakes. Most of these mutations are detrimental – they reduce a virus’s ability to replicate – but some may allow a virus to replicate faster or better in human cells. Variant viruses with these rare, beneficial mutations will spread better than other variants and therefore come to dominate the viral population – that is <a href="https://www.amnh.org/exhibitions/darwin/evolution-today/natural-selection-vista">how natural selection works</a>.</p>
<p>If these viruses can replicate even a little bit within people, they have the potential to adapt and thereby thrive in their new human hosts. That is nature’s gain-of-function experiment, and <a href="https://doi.org/10.1093/ve/veaa016">it is</a> <a href="https://doi.org/10.1016/j.chom.2020.08.011">happening constantly</a>.</p>
<p>Gain-of-function experiments in the lab can help scientists <a href="https://doi.org/10.1126%2Fscience.1222526">anticipate the changes</a> viruses may undergo in nature by understanding what specific features allow them to transmit between people and infect them. In contrast to nature’s experiments, these are conducted in <a href="https://www.cdc.gov/labs/BMBL.html">highly controlled lab conditions</a> designed to limit infection risk to laboratory personnel and others, including air flow control, personal protective equipment and waste sterilization.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/523674/original/file-20230501-20-lxf4la.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="People in protective clothing collecting dead pelicans on a beach" src="https://images.theconversation.com/files/523674/original/file-20230501-20-lxf4la.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/523674/original/file-20230501-20-lxf4la.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/523674/original/file-20230501-20-lxf4la.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/523674/original/file-20230501-20-lxf4la.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/523674/original/file-20230501-20-lxf4la.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/523674/original/file-20230501-20-lxf4la.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/523674/original/file-20230501-20-lxf4la.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Researchers and public health officials are concerned that the bird flu virus is evolving to more readily infect people.</span>
<span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/BirdFluMutations/6895d38a33de468c93c14da427b4dfff">Guadalupe Pardo/AP Photo</a></span>
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</figure>
<p>It is important that researchers carefully observe lab safety to minimize the theoretical risk of infecting the general population. It is equally important that virologists continue to apply the tools of modern science to gauge the risk of natural viral spillovers before they become outbreaks. </p>
<p>A <a href="https://theconversation.com/as-bird-flu-continues-to-spread-in-the-us-and-worldwide-whats-the-risk-that-it-could-start-a-human-pandemic-4-questions-answered-200204">bird flu outbreak</a> is currently raging across multiple continents. While the H5N1 virus is primarily infecting birds, some people have gotten sick too. More spillover events can change the virus in ways that would allow it to <a href="https://doi.org/10.1126/science.adi1013">transmit more efficiently among people</a>, potentially leading to a pandemic. </p>
<p>Scientists have a better appreciation of the tangible risk of bird flu spillover because of <a href="https://doi.org/10.1126/science.1213362">gain-of-function experiments</a> <a href="https://doi.org/10.1038/nature10831">published a decade ago</a>. Those lab studies showed that bird flu viruses could be transmitted through the air between ferrets within a few feet of one another. They also revealed multiple features of the evolutionary path the H5N1 virus would need to take before it becomes transmissible in mammals, informing what signatures researchers need to look out for during surveillance of the current outbreak.</p>
<h2>Oversight on gain of function</h2>
<p>Perhaps this sounds like a semantic argument, and in many respects it is. <a href="https://www.statnews.com/2021/12/23/gain-of-function-research-advances-knowledge-and-saves-lives/">Many researchers</a> would likely agree that gain of function as a general tool is an important way to study biology that should not be restricted, while also arguing that it should be curtailed for research on specific dangerous pathogens. The problem with this argument is that pathogen research needs to include gain-of-function approaches in order to be effective – just as in any area of biology.</p>
<p><a href="https://doi.org/10.1128/jvi.00089-23">Oversight of gain-of-function research</a> on potential pandemic pathogens already exists. Multiple layers of safety measures at the institutional and national levels minimize the risks of virus research.</p>
<p>While updates to current oversight are not unreasonable, we believe that <a href="https://www.nih.gov/about-nih/who-we-are/nih-director/statements/statement-report-national-science-advisory-board-biosecurity">blanket bans or additional restrictions</a> on gain-of-function research do not make society safer. They may instead slow research in areas ranging from cancer therapies to agriculture. Clarifying which specific research areas are of concern regarding gain-of-function approaches can help identify how the current oversight framework can be improved.</p><img src="https://counter.theconversation.com/content/202084/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Seema Lakdawala receives funding from National Institutes of Health and the Flu Lab. </span></em></p><p class="fine-print"><em><span>Anice Lowen receives research funding from the National Institutes of Health and Flu Lab. </span></em></p>From cancer immunotherapy and antibiotics to GMO crops and pandemic surveillance, gain of function is a cornerstone of basic research.Seema Lakdawala, Associate Professor of Microbiology and Immunology at Emory University and Adjunct Professor Microbiology and Molecular Genetics, University of PittsburghAnice Lowen, Associate Professor of Microbiology and Immunology, Emory UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2002242023-02-23T21:32:26Z2023-02-23T21:32:26ZThe fungus zombies in ‘The Last of Us’ are fictional, but real fungi can infect people, and they’re becoming more resistant<figure><img src="https://images.theconversation.com/files/511892/original/file-20230223-22-69v4bj.jpeg?ixlib=rb-1.1.0&rect=250%2C14%2C1667%2C1063&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">In the HBO series ‘The Last of Us,’ the parasitic fungus cordyeps mutates, and jumps from insects to humans and quickly spreads around the world, rendering its victims helpless to control their thoughts and actions.</span> <span class="attribution"><span class="source">(HBO)</span></span></figcaption></figure><p>Many of the people watching <a href="https://www.hbo.com/the-last-of-us"><em>The Last of Us</em></a> are likely there for the zombies.</p>
<p>I love the zombies too, but I’m really there for the fungus.</p>
<p>I’ve been studying fungi since my PhD work in the 1980s, and I grow more fascinated by these amazing organisms with every passing year.</p>
<p>In the HBO series and the <a href="https://www.playstation.com/en-ca/games/the-last-of-us-part-i/">video game that inspired it</a>, a parasitic fungus — a fictitious mutation of the <a href="https://www.nationalgeographic.com/animals/article/cordyceps-zombie-fungus-takes-over-ants">very real cordyceps</a> — jumps from insects to humans and quickly spreads around the world, rendering its victims helpless to control their thoughts and actions. Far-fetched fungal fear-mongering? It’s definitely fictional, but maybe not as preposterous as it might seem.</p>
<h2>Fascinating fungi</h2>
<p>From microscopic mould spores to <a href="https://www.scientificamerican.com/article/strange-but-true-largest-organism-is-fungus/">kilometres-long mycelium</a> under the forest floor, members of this distinct biological kingdom — neither plant nor animal — are incredible, and highly worthy of more attention.</p>
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<a href="https://images.theconversation.com/files/512053/original/file-20230223-16-mssl7i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="An ant with fungal growths growing from its head and abdomen, on a green leaf" src="https://images.theconversation.com/files/512053/original/file-20230223-16-mssl7i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/512053/original/file-20230223-16-mssl7i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/512053/original/file-20230223-16-mssl7i.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/512053/original/file-20230223-16-mssl7i.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/512053/original/file-20230223-16-mssl7i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/512053/original/file-20230223-16-mssl7i.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/512053/original/file-20230223-16-mssl7i.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=502&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">An ant infected with parasitic cordyceps fungus.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
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<p>Most of us may not think about them beyond the mushroom slices on our pizza, but fungi figure prominently in our everyday lives. Do you eat bread? Thank <a href="https://www.britannica.com/science/yeast-fungus">the fungus we call yeast</a>. Do you enjoy beer, wine or whisky? Raise a glass to your <a href="https://doi.org/10.3390%2Fmicroorganisms8081142">fungal friends responsible for the fermentation</a> that brings them to life.</p>
<p>Every time a round of antibiotics helps you recover from some form of infection, remember that <a href="https://www.acs.org/education/whatischemistry/landmarks/flemingpenicillin.html">a mould gave us the compounds that became penicillin</a> and its many derivatives.</p>
<p>Fungi are incredible chemists. They make many compounds that humans cannot easily replicate in the lab. Some make compounds that can affect behaviour. </p>
<p>Look at <a href="https://www.camh.ca/en/health-info/mental-illness-and-addiction-index/lsd">lysergic acid diethylamide</a>, commonly known as LSD, or “acid.” Its well-known psychedelic effects originate from a grain mould. Similarly, “magic” mushrooms are the source of <a href="https://www.canada.ca/en/health-canada/services/substance-use/controlled-illegal-drugs/magic-mushrooms.html">psilocybin</a>. LSD and magic mushrooms are both illegal recreational drugs but are also under study for their therapeutic value.</p>
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Read more:
<a href="https://theconversation.com/albertas-new-policy-on-psychedelic-drug-treatment-for-mental-illness-will-canada-lead-the-psychedelic-renaissance-195061">Alberta’s new policy on psychedelic drug treatment for mental illness: Will Canada lead the psychedelic renaissance?</a>
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<h2>Fungal infections</h2>
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<a href="https://images.theconversation.com/files/511900/original/file-20230223-2553-wdgm71.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Pink flower-like blooms on translucent stems" src="https://images.theconversation.com/files/511900/original/file-20230223-2553-wdgm71.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/511900/original/file-20230223-2553-wdgm71.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=566&fit=crop&dpr=1 600w, https://images.theconversation.com/files/511900/original/file-20230223-2553-wdgm71.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=566&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/511900/original/file-20230223-2553-wdgm71.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=566&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/511900/original/file-20230223-2553-wdgm71.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=711&fit=crop&dpr=1 754w, https://images.theconversation.com/files/511900/original/file-20230223-2553-wdgm71.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=711&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/511900/original/file-20230223-2553-wdgm71.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=711&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Microscopic image of the fungus Aspergillus fumigatus.</span>
<span class="attribution"><span class="source">(CDC)</span></span>
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<p>Fungi also have an aggressive side. Apart from breaking down dead plants and animals, some forms attack living creatures, including humans. Whole pharmacy shelves are stocked with remedies for <a href="https://www.cdc.gov/healthywater/hygiene/disease/athletes_foot.html">athlete’s foot</a>, <a href="https://www.cdc.gov/fungal/diseases/candidiasis/index.html">yeast infections</a> and <a href="https://www.cdc.gov/fungal/diseases/ringworm/treatment.html">jock itch</a>, all of them nasty fungal infections. Even <a href="https://doi.org/10.1016/j.jaad.2004.10.211">dandruff is caused by a fungus</a>.</p>
<p>Yet while we can access an array of medications to cure bacterial infections such as pneumonia and strep throat, there are only <a href="https://www.healthline.com/health/fungal-infection/antifungal">four known compounds</a> available to rid ourselves of fungal infections. Three are available in the various over-the-counter powders, sprays and ointments we use to treat common fungal infections. </p>
<p>The fourth and newest class, echinocandins, is reserved for hospital settings, where the consequences of fungal infections can be deadly.</p>
<p><a href="https://www.thewrightlab.com/">My team’s research lab</a> at McMaster is part of the university’s broader <a href="https://globalnexus.mcmaster.ca/">Global Nexus for Pandemics and Biological Threats</a>, and also works with the global research organization CIFAR’s <a href="https://cifar.ca/research-programs/fungal-kingdom/">Fungal Kingdom: Threats and Opportunities</a> program. </p>
<p>We are working to find ways to limit the potential harm humans face from fungal infections. We also seek to understand how we can use their abundant and as-yet barely tapped potential to make new antibiotics <a href="https://theconversation.com/antibiotic-resistant-infections-could-destroy-our-way-of-life-new-report-126670">before we lose the waning power of penicillin and its derivatives</a>.</p>
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<em>
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Read more:
<a href="https://theconversation.com/future-infectious-diseases-recent-history-shows-we-can-never-again-be-complacent-about-pathogens-177746">Future infectious diseases: Recent history shows we can never again be complacent about pathogens</a>
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<h2>Fungi adapt and evolve</h2>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/512055/original/file-20230223-28-etvxfk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Blue organisms growing from a translucent stalk" src="https://images.theconversation.com/files/512055/original/file-20230223-28-etvxfk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/512055/original/file-20230223-28-etvxfk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=414&fit=crop&dpr=1 600w, https://images.theconversation.com/files/512055/original/file-20230223-28-etvxfk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=414&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/512055/original/file-20230223-28-etvxfk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=414&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/512055/original/file-20230223-28-etvxfk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=520&fit=crop&dpr=1 754w, https://images.theconversation.com/files/512055/original/file-20230223-28-etvxfk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=520&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/512055/original/file-20230223-28-etvxfk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=520&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Microscopic image of the fungal organism, Epidermophyton floccosum, which is a cause of infections such as athlete’s foot and jock itch.</span>
<span class="attribution"><span class="source">(CDC/Libero Ajello)</span></span>
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</figure>
<p>I was first attracted to fungus research as a student about to begin my PhD studies about 35 years ago. At that time, <a href="https://www.hiv.gov/hiv-basics/overview/history/hiv-and-aids-timeline">HIV-AIDS was still emerging</a>, shutting down the immune systems of otherwise healthy people, leaving them vulnerable to opportunistic infections, <a href="https://www.cdc.gov/fungal/infections/hiv-aids.html">including fungal infections</a>.</p>
<p>I wanted to understand more about how fungi worked.</p>
<p>Like bacteria and viruses, fungi are always evolving and adapting, <a href="https://www.who.int/news/item/25-10-2022-who-releases-first-ever-list-of-health-threatening-fungi">finding ways to survive under hostile conditions</a>. We are seeing many forms of fungi adapting to live at ever-higher temperatures, including body temperature, which has long been humans’ first line of defence.</p>
<p>We are also seeing growing antimicrobial resistance among some causes of fungal infection, yeasts such as <a href="https://cifar.ca/cifarnews/2019/04/30/tackling-a-global-superbug/">Candida auris</a> and moulds such as <a href="https://www.cdc.gov/fungal/diseases/aspergillosis/index.html">Aspergillus</a>, both of which can be causes of in-hospital infections.</p>
<h2>Potential for a fungal pandemic</h2>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/E5tSO9aR2Ds?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">In the HBO Max drama ‘The Last of Us,’ a fungal infection turns its victims into fungus-sprouting zombies.</span></figcaption>
</figure>
<p>While <em>The Last of Us</em> is a strictly dramatic projection of what might happen in a deadly fungal outbreak, it is at least based, if not in reality, in logic.</p>
<p>Fungi are able to influence perceptions and behaviour through chemistry. Are they getting closer? You bet. Do they make zombies? Not that we know of, but the thought is darkly entertaining, and that keeps me watching.</p>
<p>The show does do an excellent service by reminding us that we need to adapt to stay ahead of the possibility of a fungal pandemic.</p>
<p>In the same way the movie <em><a href="https://mediashift.org/2017/04/reading-presidents-men-age-trump/">All The President’s Men</a></em> once inspired a generation of journalists, and <em><a href="https://news.harvard.edu/gazette/story/2012/10/the-paper-chase-at-40/">The Paper Chase</a></em> later channelled many eager students toward law school, I am hopeful that <em>The Last of Us</em> may trigger new interest in studying fungi.</p>
<p>The more minds we can focus on unlocking the true magic in mushrooms, the better off we’ll all be.</p><img src="https://counter.theconversation.com/content/200224/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Gerry Wright receives funding for antifungal research from the Canadian Institutes of Health Research and the Canadian Institute for the Advanced Research and is a consultant for Kapoose Creek, a Canadian biotechnology firm.</span></em></p>While ‘The Last of Us’ is a dramatic projection of a deadly fungal outbreak, it is based, if not in reality, in logic. And it’s a reminder that fungal infections are growing more resistant.Gerry Wright, Professor of Biochemistry and Biomedical Sciences, McMaster UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1987092023-02-09T18:58:21Z2023-02-09T18:58:21ZThe fight against antibiotic resistance is growing more urgent, but artificial intelligence can help<figure><img src="https://images.theconversation.com/files/506943/original/file-20230129-39252-82ujl8.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C3840%2C2160&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Artificial intelligence can be used to develop new drugs, quickly and cheaply.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>Since the discovery of penicillin in the late 1920s, antibiotics have “<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378521/">revolutionized medicine and saved millions of lives</a>.” Unfortunately, the effectiveness of antibiotics is now threatened by <a href="https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance">the increase of antibiotic-resistant bacteria globally</a>.</p>
<p>Antibiotic-resistant infections cause the deaths of up to <a href="https://www.ox.ac.uk/news/2022-01-20-estimated-12-million-people-died-2019-antibiotic-resistant-bacterial-infections">1.2 million people annually</a>, making them one of the leading causes of death. </p>
<p>There are several factors contributing to this crisis of resistance to antibiotics. These <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378521/">include overusing and misusing antibiotics in treatments</a>. In addition, pharmaceutical companies are <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378521/">over-regulated and disincentivized from developing new drugs</a>.</p>
<p>The World Health Organization estimates that <a href="https://www.who.int/news/item/29-04-2019-new-report-calls-for-urgent-action-to-avert-antimicrobial-resistance-crisis">10 million people will die from such infections by the year 2050</a>. </p>
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Read more:
<a href="https://theconversation.com/jeff-beck-dies-of-bacterial-meningitis-what-you-need-to-know-about-the-disease-197721">Jeff Beck dies of bacterial meningitis – what you need to know about the disease</a>
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<p>The impacts of antibiotic-resistant infections are wide-ranging. In the absence of effective prevention and treatment for bacterial infections, medical procedures such as organ transplants, chemotherapy and caesarean sections become far riskier. That’s <a href="https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance">because the severity of bacteria-related infections is increasing</a> and untreated infections can cause a variety of health problems.</p>
<h2>Discovering new antibiotics</h2>
<p>Antibiotics treat illnesses by attacking the bacteria that cause them <a href="https://www.medicalnewstoday.com/articles/10278#what-are-they">by destroying them or preventing them from reproducing</a>. </p>
<p>The discovery of new antibiotics has the potential to save millions of lives. The last discovery of a <a href="https://www.pewtrusts.org/en/research-and-analysis/articles/2021/02/18/researcher-explains-challenges-in-finding-novel-antibiotics">novel class of antibiotics was in 1984</a>. But it’s not easy to find a truly new antibiotic: <a href="https://wellcome.org/news/why-is-it-so-hard-develop-new-antibiotics">only one out of every 15 antibiotics that enter pre-clinical development reach patients</a>.</p>
<p>Developing a new drug is a costly, and often lengthy process. Also, the process of bringing novel drugs to the market and making them accessible presents formidable challenges.</p>
<p>This is where artificial intelligence (AI) comes into play, because it allows researchers to quickly and accurately design and assess potential drugs.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/509234/original/file-20230209-28-dfh4qg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="a shelf of packaged medications, the hands of someone wearing a white coat and holding a pill packet are visible" src="https://images.theconversation.com/files/509234/original/file-20230209-28-dfh4qg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/509234/original/file-20230209-28-dfh4qg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=377&fit=crop&dpr=1 600w, https://images.theconversation.com/files/509234/original/file-20230209-28-dfh4qg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=377&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/509234/original/file-20230209-28-dfh4qg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=377&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/509234/original/file-20230209-28-dfh4qg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=474&fit=crop&dpr=1 754w, https://images.theconversation.com/files/509234/original/file-20230209-28-dfh4qg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=474&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/509234/original/file-20230209-28-dfh4qg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=474&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Getting a new drug from development to market is a costly, and often lengthy process.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
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<h2>The role of AI in drug design</h2>
<p>There has been an explosion in research in recent years in <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626864/">the use of AI for drug design and discovery</a>. AI can identify new antibiotics that are structurally distinct from currently available ones and effective against a range of bacteria. </p>
<p>In order to discover more effective antibiotics, we need to understand the structural basis of resistance, and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944398/">this understanding enables rational design principles</a>. Developing effective second-generation antibiotics often involves optimizing first-generation drugs.</p>
<p>In drug development, a significant amount of money is spent developing and evaluating each generation of compounds. Researchers can use AI tools to teach computers themselves to find quick and cheap ways of discovering such novel medications.</p>
<p>Artificial intelligence is already showing promising results in <a href="https://news.mit.edu/2020/artificial-intelligence-identifies-new-antibiotic-0220">finding new antibiotics</a>. In 2019, researchers used a deep learning approach to identify the wide-spectrum antibiotic Halicin. Halicin had previously <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2667321/">failed clinical trials as a treatment for diabetes</a>, but AI suggested a different application.</p>
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<p>Given the early identification of such a potentially strong antibiotic using artificial intelligence, a large number of such broad-spectrum antibiotics that could be effective against a range of bacteria might be identified. These drugs still need to undergo clinical trials.</p>
<p>Researchers at the U.S. National Institutes of Health harnessed AI’s predictive power to demonstrate <a href="https://www.embopress.org/doi/full/10.15252/msb.202211081">AI’s potential to accelerate the process of selecting future antibiotics</a>.</p>
<p>AI can be trained to screen and discover new drugs much faster — <a href="https://mansbach-lab.github.io/research/">our lab at Concordia University</a> is using this approach to identify antibiotics that would target bacterial RNA. </p>
<h2>Algorithmic learning</h2>
<p>Researchers design an algorithm that uses data from databases <a href="https://zinc.docking.org/">like ZINC</a> (a collection of commercially available chemicals that can be used for virtual screening) to figure out how molecules and their properties relate. The AI models extract information from the database to analyze their patterns. </p>
<p>The models created by the algorithm are <a href="https://directorsblog.nih.gov/2022/09/13/using-ai-to-find-new-antibiotics-still-a-work-in-progress/">trained on pre-existing data</a>. AI can rapidly sift through huge amounts of data to understand important patterns in the content or structure of a molecule. </p>
<p>We have seen the potential of current models to <a href="https://aimagazine.com/articles/deepminds-alphafold-joins-ai-search-for-new-antibiotics">correctly predict how bacterial proteins and anti-bacterial agents would interact</a>. But in order to maximize AI’s predictive capabilities, further refinement will still be required. </p>
<h2>Limitations of AI</h2>
<p>Researchers <a href="https://www.brookings.edu/research/how-artificial-intelligence-is-transforming-the-world/">haven’t yet explored the full potential of AI models</a>. With further developments, like increased computing power, AI can become an important tool in science. The development of AI in drug discovery research, as well as finding new antibiotics to treat bacterial infections is a work in progress. </p>
<p>The ability of <a href="https://directorsblog.nih.gov/2022/09/13/using-ai-to-find-new-antibiotics-still-a-work-in-progress/">artificial intelligence to predict and accurately identify</a> leads has shown promising results. </p>
<p>Even when powered by powerful AI approaches, finding new drugs will not be easy. We need to understand that AI is a tool that contributes to research by identifying or predicting an outcome of a research question. </p>
<p>AI is implemented in a number of industries today, and is already changing the world. But it’s not a replacement for a scientist or doctor. AI can help the researcher to enhance or fast-track the process of drug discovery.</p>
<p>Even though we still have a way to go before we can fully utilize this method, there is no doubt that AI will significantly change how drugs are discovered and developed.</p><img src="https://counter.theconversation.com/content/198709/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Vrinda’s doctoral research is funded by the Natural Sciences and Engineering Research Council of Canada (NSERC), Canada Research Chairs and Concordia University. She currently works with Molecular Forecaster and has received Mitacs Accelerate Fellowship for her internship project. </span></em></p><p class="fine-print"><em><span>Rachael (Ré) A Mansbach receives funding from NSERC through Discovery Grant #RGPIN-2021-03470 and a Tier II Canada Research Chair in Computational Biophysics. They also work with Molecular Forecaster through a funded Mitacs grant.</span></em></p>Bacterial infections are a growing global challenge. This is due to antibiotic-resistant bacteria, and researchers are turning to AI to develop new drugs.Vrinda Nair, Doctoral Student in Physics, Concordia UniversityRachael (Ré) A Mansbach, Assistant professor, Physics, Concordia UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1965402022-12-16T16:18:51Z2022-12-16T16:18:51ZAntibiotics shortages: what’s causing them and how countries can minimise the impact<figure><img src="https://images.theconversation.com/files/501500/original/file-20221216-19-9xjslg.jpg?ixlib=rb-1.1.0&rect=63%2C0%2C7097%2C4459&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/pharmacist-holding-medicine-box-capsule-pack-704036482">i viewfinder/Shutterstock</a></span></figcaption></figure><p>A variety of antibiotics are currently in short supply <a href="https://www.wsj.com/articles/europe-is-hit-by-shortages-of-antibiotics-11670639357">across Europe</a>. In <a href="https://www.ft.com/content/10688692-57c5-4c84-a333-789df699be6e">the UK</a>, for example, the availability of amoxicillin and penicillin, which are used to treat infections such as strep A, is low.</p>
<p>Medicine shortages are a significant problem around the world, affecting patient welfare and costs of care. A 2021 survey of community pharmacists <a href="https://www.pgeu.eu/publications/press-release-pgeu-medicine-shortages-survey-2021-results/">in 27 European countries</a> confirmed that shortages are a persisting issue. </p>
<p>The current shortage of antibiotics could have negative effects on patients and raises public health concerns. So what’s causing these shortages, and what can we do to ensure people who need antibiotics can access the right ones?</p>
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Read more:
<a href="https://theconversation.com/strep-a-three-doctors-explain-what-you-need-to-look-out-for-195972">Strep A: three doctors explain what you need to look out for</a>
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<p>Our <a href="https://www.bi.edu/research/centres-groups-and-other-initiatives/mia/">research on medicine shortages</a> suggests that antibiotics supply problems are, in many respects, no different from other recent instances of <a href="https://www.bmj.com/content/377/bmj.o1183">drug shortages</a>. They are the result of well-known demand and supply issues.</p>
<p>On the demand side, <a href="https://www.ft.com/content/10688692-57c5-4c84-a333-789df699be6e">changing infection patterns</a> and possibly also the continuing cold snap have contributed to higher than usual use of antibiotics. </p>
<p>In the UK, for example, medical experts have explained that cases of scarlet fever and strep A usually increase <a href="https://ukhsa-newsroom.prgloo.com/news/ukhsa-update-on-scarlet-fever-and-invasive-group-a-strep-3">in the new year</a>. But altered immunity levels in the population related to the COVID pandemic seem to have influenced infection cycles. </p>
<p>The earlier than usual spike in illness was largely unexpected, invalidating demand forecasts and disrupting manufacturers’ production plans. Accordingly, pharmacies have reported difficulties <a href="https://www.theguardian.com/society/2022/dec/09/parents-report-struggle-to-find-antibiotics-uk-strep-a-cases-rise">securing supplies</a> of key antibiotics to meet the spike in demand.</p>
<p>In addition, changing prescription patterns can contribute to demand spikes. A <a href="https://www.theguardian.com/society/2022/dec/06/children-risk-strep-a-england-preventive-antibiotics">recent change of advice</a> in England permitted the use of antibiotics for children at risk of strep A as a “blanket measure”, which in turn likely increased demand for penicillin and amoxicillin. </p>
<p>On the supply side, over-reliance on a small number of suppliers for active pharmaceutical ingredients and other raw materials has made it difficult for manufacturers to match current demand. A specific challenge has been <a href="https://www.wsj.com/articles/europe-is-hit-by-shortages-of-antibiotics-11670639357">China’s zero COVID policy</a> and the constraints this has placed on manufacturing output and logistics.</p>
<p>More broadly, heavy dependence on certain countries as key sources for ingredients and raw materials is a significant issue. China and India together accounted for <a href="https://asia.nikkei.com/static/vdata/infographics/chinavaccine-3/">more than 60%</a> of the supply of active pharmaceutical ingredients globally in 2020. This level of supply market concentration can lead to severe availability issues when medicine supply chains are disrupted.</p>
<p>Another key issue is that many antibiotics, especially those that are not protected by patents (widely known as “generics”), are very cheap. Although low prices make these antibiotics affordable, they also reduce the financial attractiveness for manufacturers, who may decide to discontinue production when supplying these products no longer makes economic sense.</p>
<p>Rising energy costs <a href="https://www.wsj.com/articles/europe-is-hit-by-shortages-of-antibiotics-11670639357">exacerbate these challenges</a> because they increase production costs, which has contributed to some antibiotics manufacturers ceasing production.</p>
<h2>Problems for patients</h2>
<p>If people can’t access the antibiotics they need, this will lead to more cases of severe illness. In very serious cases, it could be life-threatening.</p>
<p>The majority of amoxicillin- and penicillin-based products are “narrow-spectrum” antibiotics, meaning that they target a specific set of infections. Shortages of these products could increase the use of “broad-spectrum” antibiotics, which are meant to treat a host of bacterial infections.</p>
<p>Although this is better than leaving infections untreated, <a href="https://www.reactgroup.org/toolbox/understand/antibiotics/how-do-antibiotics-work/">broad-spectrum antibiotics</a> elevate the risk of antimicrobial resistance, making it more challenging to treat infections in the long run.</p>
<figure class="align-center ">
<img alt="A man feels his daughter's forehead, holding a thermometer." src="https://images.theconversation.com/files/501501/original/file-20221216-22-w5sujv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/501501/original/file-20221216-22-w5sujv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/501501/original/file-20221216-22-w5sujv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/501501/original/file-20221216-22-w5sujv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/501501/original/file-20221216-22-w5sujv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/501501/original/file-20221216-22-w5sujv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/501501/original/file-20221216-22-w5sujv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">There’s been a big increase in the number of children with Strep A in the UK recently.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/sick-little-girl-covered-blanket-lying-561769342">George Rudy/Shutterstock</a></span>
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<h2>What can be done?</h2>
<p>Given the public health risks involved, it’s imperative that antibiotics go to patients who need them today, instead of being held for patients who might need them tomorrow.</p>
<p>An immediate action for governments to take is to actively discourage hoarding by individuals and healthcare professionals to ease demand pressures. The <a href="https://www.pulsetoday.co.uk/news/clinical-areas/paediatrics/government-attempts-to-ease-antibiotics-shortage-with-hoarding-ban/">UK government</a> has already taken steps in this direction. On the pharmacy side, rather than build emergency stocks, pharmacies could exchange information about their stock levels and collaborate to share stock as and when needed.</p>
<p>Governments reimbursing pharmacies for costs associated with <a href="https://amp-theguardian-com.cdn.ampproject.org/c/s/amp.theguardian.com/society/2022/dec/13/uk-pharmacists-report-sharp-rise-in-prices-for-strep-a-antibiotics?utm_source=upday&utm_medium=referral">antibiotics price increases</a>, to ensure they maintain a healthy profit margin, can contribute to supply continuity. Medical experts could also review prescription guidelines so that use of antibiotics is encouraged only in cases where serious health consequences are expected. This would help to manage demand more effectively. </p>
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<strong>
Read more:
<a href="https://theconversation.com/heres-why-so-many-medications-are-out-of-stock-and-what-to-do-if-it-affects-you-190476">Here’s why so many medications are out of stock — and what to do if it affects you</a>
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<p>Governments also need to work with manufacturers and wholesalers to review their stockpiling policies. Investing in suitably-sized buffer stocks of antibiotics to account for seasonal spikes in demand can help suppliers and healthcare professionals buy time when imbalances between supply and demand occur. Any cost increases associated with supply chain actors holding safety stocks could be covered either through direct government payments or product price increases. </p>
<p>Ultimately, though, fixing medicine shortages requires rethinking procurement systems to incentivise supply security and reducing dependence on remote suppliers of active ingredients and raw materials. The latter might, for instance, involve joint investment in regional manufacturing hubs in Europe.</p><img src="https://counter.theconversation.com/content/196540/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Kostas Selviaridis has received funding from the Research Council of Norway for the research project "Measures for Improving Availability of medicines and vaccines" (MIA). </span></em></p><p class="fine-print"><em><span>Nonhlanhla Dube has received funding from the Research Council of Norway for research on "Measures for Improved Availability of medicines and vaccines" (MIA). </span></em></p>These shortages are a result of rising demand and supply chain bottlenecks. But there are things that can be done to reduce harms to public health.Kostas Selviaridis, Senior Lecturer in Operations Management, Department of Management Science, Lancaster UniversityNonhlanhla Dube, Lecturer in Operations Management, Lancaster UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1769632022-07-27T12:00:00Z2022-07-27T12:00:00ZNature is the world’s original pharmacy – returning to medicine’s roots could help fill drug discovery gaps<figure><img src="https://images.theconversation.com/files/475941/original/file-20220725-19-fgfrya.jpg?ixlib=rb-1.1.0&rect=98%2C165%2C1986%2C1237&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Around 75% of antibiotics, including penicillin and amphotericin B, are derived from natural products.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/directly-above-shot-of-pills-on-leaf-royalty-free-image/1004440852">Aphiwat Chuangchoem/EyeEm via Getty Images</a></span></figcaption></figure><p>While humans evolved over a period of approximately <a href="https://humanorigins.si.edu/education/introduction-human-evolution">6 million years</a>, breakthroughs in modern medicine as we know it today got going only in the <a href="https://www.medicalnewstoday.com/articles/323538">19th and 20th centuries</a>. So how did humans successfully survive through millions of years of diseases and illnesses without modern drugs and treatments?</p>
<p>This was a question I came to wonder about when the COVID-19 pandemic reached my family in India in April 2020, when there was very limited access to vaccines and treatments. All of my years working as a <a href="https://scholar.google.com/citations?user=8_T1ueYAAAAJ&hl=en">biomedical scientist</a>, requiring empirical evidence and formal safety testing before using a treatment, took a back seat as I scrambled for potential therapies from any sources I could find, be it scientific papers or folklore. I was ready to try any experimental or traditional medicine that might have a chance at helping my dad.</p>
<p>Luckily, my dad recovered. I can’t say for sure if any of the traditional medicines we used actually helped him recover. But as someone whose entire scientific career has focused on discovering new drugs from chemical compounds found in nature, I wondered if there was a molecule in the traditional medicines we used that could be isolated and optimized to treat COVID-19.</p>
<p>Scientists like me have been looking for new drugs for various diseases by purifying existing compounds in nature instead of synthesizing completely new ones in the lab. From <a href="https://doi.org/10.1021/acs.jnatprod.0c00968">COVID-19</a> to <a href="https://doi.org/10.1007/978-3-319-78538-7_17">antibiotic resistance</a>, I believe that past successes and new technologies point to the tremendous potential of developing new drugs from natural products.</p>
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<figcaption><span class="caption">Early drug development involved searching for plants with medicinal properties. Scientists have since been able to isolate the active ingredients bestowing medicinal properties on natural products, such as the morphine in poppies.</span></figcaption>
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<h2>The natural product advantage</h2>
<p>Humans have coevolved with the rest of nature over time, and obtaining medicine is perhaps one of the most important interactions people continue to have with the natural world. DNA analyses have shown that <a href="https://doi.org/10.1038/nature21674">early humans may have treated dental abscesses</a> with poplar, containing the active ingredient of aspirin, and <em>Penicillium</em> mold, containing the antibiotic penicillin.</p>
<p>Researchers call the molecules like the ones that give poplar and <em>Penicillium</em> their biological effects <a href="https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Book%3A_Basic_Principles_of_Organic_Chemistry_(Roberts_and_Caserio)/30%3A_Natural_Products_and_Biosynthesis">natural products</a> because they are produced by living organisms such as microbes, fungi, corals and plants. These natural products have evolved to be <a href="https://doi.org/10.1002/1521-3773(20020816)41:16%3C2878::AID-ANIE2878%3E3.0.CO;2-B">structurally “optimized</a>” to serve particular biological functions, primarily to <a href="https://pubs.rsc.org/en/content/articlelanding/2015/np/c4np00150h">deter predators or gain a survival advantage</a> in a particular environment and over other competitors.</p>
<p>Because natural products are already made to function in living creatures, this makes them especially attractive as a source for drug discovery. While proteins may look different in different organisms, many have <a href="https://doi.org/10.1073/pnas.95.18.10396">similar structural features and functions</a> across species. This can help ease the search for related proteins that work in people.</p>
<h2>Natural product hall of fame</h2>
<p>Natural products derived from microbes and plants are the biggest resource for drug discovery for modern medicine. Case in point, the discovery of the antibiotic <a href="https://www.acs.org/content/acs/en/education/whatischemistry/landmarks/flemingpenicillin.html">penicillin</a> in 1940 from <em>Penicillium</em> mold allowed doctors to treat previously fatal infections and started the era of antibiotics. </p>
<p>As of September 2019, <a href="https://doi.org/10.1021/acs.jnatprod.9b01285">over 50%</a> of currently available FDA-approved drugs are either directly or indirectly derived from natural products. One of the best-selling drugs of the past two decades, atorvastatin (Lipitor), an anti-cholesterol drug, is derived from a compound produced by the fungus <a href="https://doi.org/10.1038/nm1008-1050"><em>Penicillium citrinum</em></a>. From 1992 to 2017, atorvastatin sales in the U.S. totaled <a href="https://www.fiercepharma.com/pharma/from-old-behemoth-lipitor-to-new-king-humira-u-s-best-selling-drugs-over-25-years">US$94.67 billion</a>.</p>
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<figcaption><span class="caption">Penicillin revolutionized medicine.</span></figcaption>
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<p>Other prominent examples of drugs derived from natural products currently used today include the anti-fungal <a href="https://doi.org/10.1378/chest.54.Supplement_1.296">amphotericin B</a>, isolated from the soil bacteria <em>Streptomyces nodosus</em>, the chemotherapy <a href="https://www.acs.org/content/acs/en/education/whatischemistry/landmarks/camptothecintaxol.html">taxol</a>, isolated from the bark of the Pacific yew tree, and the immunosuppressant <a href="https://doi.org/10.1016/S0269-915X(98)80100-6">cyclosporin</a>, isolated from the fungus <em>Tolypocladium inflatum</em>.</p>
<p>I believe that undiscovered treatments for a wide range of diseases are lying right under our noses in natural products. In January 2021, the FDA approved <a href="https://www.lupus.org/resources/lupkynis-voclosporin-what-you-need-to-know">voclosporin (Lupkynis)</a>, isolated from the fungus <a href="https://mycocosm.jgi.doe.gov/Tolinf1/Tolinf1.home.html"><em>Tolypocladium inflatum</em></a>, to treat lupus. Recently, researchers have been looking into <a href="https://doi.org/10.1126/sciadv.abi6110">cannabidiol</a> and other <a href="https://doi.org/10.1021/acs.jnatprod.1c00946">cannabinoid compounds</a> as a potential way to prevent or treat COVID-19. The FDA has not authorized any drug containing CBD for COVID-19 yet.</p>
<h2>Challenges in natural product discovery</h2>
<p>Researchers are increasingly able to use new <a href="https://doi.org/10.1038/s41573-020-00114-z">screening technologies and methods</a> to isolate previously unidentified natural products. Screening for natural products typically involves looking through a large library of extracts from natural sources. The <a href="https://www.lsi.umich.edu/science/centers-technologies/natural-products-discovery-core">Natural Product Drug Discovery Core</a>, which I co-founded with my colleague <a href="https://scholar.google.com/citations?user=g9dFOKIAAAAJ&hl=en">David Sherman</a> at the University of Michigan, for example, searches for potential drug targets in a library containing around 50,000 natural product extracts that each contain 30 to 50 molecules to test.</p>
<p>However, discovering natural product-based drugs is not without challenges. <a href="https://doi.org/10.1073/pnas.1614680114">Since the 1980s</a>, natural products have fallen out of favor because of a number of challenges. These include difficulty accessing expensive screening methods, and limitations in technology that isn’t able to fully analyze the complexity of natural products. There are also <a href="https://doi.org/10.1007/s11101-014-9367-z">ecological and legal considerations</a>, such as accessing samples sustainably and maintaining biodiversity. Pharmaceutical companies have <a href="https://doi.org/10.1002/0471141755.ph0911s46">reduced their natural product-based drug discovery programs</a>, and <a href="https://doi.org/10.1093/ofid/ofaa001">federal funding</a> is also in short supply due to limited profitability.</p>
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<figcaption><span class="caption">As antibiotic resistance grows, developing new drugs and using current ones more responsibly becomes even more imperative.</span></figcaption>
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<h2>Finding new drugs in nature</h2>
<p>New drugs are often necessary for unprecedented health emergencies like COVID-19. They are also needed for a health emergency that began long before the pandemic – antibiotic resistance. </p>
<p>A <a href="https://apps.who.int/iris/handle/10665/258965">September 2017 report</a> from the World Health Organization reaffirmed that antibiotic resistance is a global health emergency that will seriously jeopardize progress in modern medicine. If current antibiotics lose their effectiveness, <a href="https://www.cdc.gov/drugresistance/about.html">common medical interventions</a> such as cesarean sections and cancer treatments may become incredibly risky. Transplantation could become virtually impossible. Antibiotic-resistant microbes were the direct cause of roughly <a href="https://doi.org/10.1016/S0140-6736(21)02724-0">1.27 million deaths in 2019</a>. Treating just six of the 18 microbes that pose an antibiotic resistance threat is estimated to cost <a href="https://www.cdc.gov/drugresistance/solutions-initiative/stories/partnership-estimates-healthcare-cost.html">over $4.6 billion annually</a> in the U.S. alone. The <a href="https://www.cdc.gov/media/releases/2022/s0712-Antimicrobial-Resistance.html">COVID-19 pandemic has reversed prior progress addressing this issue</a>, with a 15% increase in antimicrobial-resistant infections from 2019 to 2020. In contrast, antimicrobial-resistant infections had fallen by 27% from 2012 to 2017. Among the likely causes of this backslide were increases in antibiotic use, difficulty following infection control guidelines and longer hospital stays.</p>
<p>As of recent estimates, <a href="https://doi.org/10.1038/ja.2017.30">roughly 75%</a> of approved antibiotics are derived from natural products. There are <a href="https://doi.org/10.1038/s41586-022-04862-3">thousands of microorganisms in the ocean</a> left to explore as potential sources of drug candidates, not to mention all the ones on land. In the search for new drugs to combat antibiotic resistance, natural products may still be the way to go.</p><img src="https://counter.theconversation.com/content/176963/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ashu Tripathi receives funding from the National Institute of Health and UM Biological Sciences Initiative. He is affiliated with the American Society of Pharmacognosy, Association of Biomolecular Resources Facilities, and Society of Industrial Microbiology and Biotechnology. </span></em></p>With the dual threats of antibiotic resistance and emerging pandemics, finding new drugs becomes even more urgent. A trove of medicines may be lying under our nose.Ashu Tripathi, Director, Natural Product Discovery Core; Assistant Professor/ Research of Medicinal Chemistry, University of MichiganLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1784632022-03-11T13:19:52Z2022-03-11T13:19:52ZGuns, not roses – here’s the true story of penicillin’s first patient<figure><img src="https://images.theconversation.com/files/451134/original/file-20220309-25-206ycs.jpg?ixlib=rb-1.1.0&rect=62%2C209%2C3357%2C2439&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Penicillin ushered in the antibiotics revolution, with amazing results during war and peace.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/in-1928-alexander-fleming-a-scottish-researcher-discovered-news-photo/90736822">Science & Society Picture Library/SSPL via Getty Images</a></span></figcaption></figure><p>Albert Alexander was dying. World War II was raging, and this police officer of the county of Oxford, England, had developed a severe case of sepsis after a cut on his face became badly infected. His blood was now teeming with deadly bacteria. </p>
<p><a href="https://doi.org/10.1136/bmj.289.6460.1721">According to his physician</a>, Charles Fletcher, Alexander was in tremendous pain, “desperately and pathetically ill.” The bacterial infection was eating him alive: He’d already lost one eye and had oozing abscesses all over his face and in his lungs.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/451124/original/file-20220309-28-1p5rh2n.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="man in 1940s police uniform" src="https://images.theconversation.com/files/451124/original/file-20220309-28-1p5rh2n.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/451124/original/file-20220309-28-1p5rh2n.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=829&fit=crop&dpr=1 600w, https://images.theconversation.com/files/451124/original/file-20220309-28-1p5rh2n.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=829&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/451124/original/file-20220309-28-1p5rh2n.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=829&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/451124/original/file-20220309-28-1p5rh2n.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1041&fit=crop&dpr=1 754w, https://images.theconversation.com/files/451124/original/file-20220309-28-1p5rh2n.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1041&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/451124/original/file-20220309-28-1p5rh2n.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1041&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Albert Alexander in uniform.</span>
<span class="attribution"><span class="source">Courtesy of Linda Willason</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>Since all known treatment options were exhausted and death appeared imminent, Fletcher decided that Alexander was the perfect candidate to try a new, experimental therapy. On Feb. 12, 1941, Alexander became the first known person to be treated with penicillin. Within days he began to make a stunning recovery.</p>
<p>I am a <a href="https://medicine.iu.edu/faculty/13502/sullivan-william">professor of pharmacology</a>, and Alexander’s story is the prelude to my yearly lecture on antibiotics. Like many other microbiology instructors, I’d always told students that Alexander’s septicemia arose after he scratched his cheek on a thorn while pruning rosebushes. This popular account dominates the scientific literature as well as recent articles and books.</p>
<p>The problem is, while descriptions of the miraculous effect of penicillin in this case are accurate, the details of Alexander’s injury were muddled, likely by wartime propaganda.</p>
<h2>Breaking the mold</h2>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/451136/original/file-20220309-13-5iedmw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="man looking into microscope" src="https://images.theconversation.com/files/451136/original/file-20220309-13-5iedmw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/451136/original/file-20220309-13-5iedmw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=672&fit=crop&dpr=1 600w, https://images.theconversation.com/files/451136/original/file-20220309-13-5iedmw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=672&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/451136/original/file-20220309-13-5iedmw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=672&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/451136/original/file-20220309-13-5iedmw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=845&fit=crop&dpr=1 754w, https://images.theconversation.com/files/451136/original/file-20220309-13-5iedmw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=845&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/451136/original/file-20220309-13-5iedmw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=845&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Bacteriologist Alexander Fleming discovered antibiotic penicillin in 1928.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/alexander-fleming-scottish-bacteriologist-18-december-1943-news-photo/102730610">Daily Herald Archive/SSPL via Getty Images</a></span>
</figcaption>
</figure>
<p>The promise of penicillin as an antibiotic was first noted in 1928, when microbiologist Alexander Fleming noticed something funny in his petri dishes at St. Mary’s Hospital in London. Fleming’s cultures of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2048009/">staphylococcal bacteria did not grow well</a> on plates contaminated with a penicillium mold. Fleming discovered that the mold’s “juice” was lethal to some types of bacteria. </p>
<p>A decade later, a team of scientists led by Howard Florey at Oxford University began the arduous task of purifying the active substance from the “mold juice” and formally testing its antimicrobial properties. In August 1940, Florey and his colleagues published their striking findings that <a href="https://doi.org/10.1016/S0140-6736(01)08728-1">purified penicillin safely wiped out numerous bacterial infections</a> in mice.</p>
<p>Florey then sought Fletcher’s help to try penicillin in a human patient. That patient would be Alexander, whose death seemed inevitable otherwise. As Fletcher stated, “There was all to gain for him in a trial of penicillin and <a href="https://doi.org/10.1136/bmj.289.6460.1721">nothing to lose</a>.”</p>
<p>At the time, purified penicillin was extremely scarce, since the mold was slow to grow and yielded precious little of the drug. Despite recycling unprocessed penicillin from Alexander’s urine, there just wasn’t enough available to finish off the infection once and for all. After 10 days of improvement, Alexander gradually relapsed. <a href="https://doi.org/10.1136/bmj.289.6460.1721">He died on March 15, 1941</a>, at the age of 43.</p>
<p>Despite the tragic outcome, Alexander’s case turbocharged interest in penicillin research. As Fletcher observed, “There was <a href="https://doi.org/10.1136/bmj.289.6460.1721">no doubt about the temporary clinical improvement</a>, and, most importantly, there had been no sort of toxic effect during the five days of continuous administration of penicillin.”</p>
<figure class="align-left zoomable">
<a href="https://images.theconversation.com/files/451131/original/file-20220309-20-mcpueg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="magazine ad with drawing of wounded soldier" src="https://images.theconversation.com/files/451131/original/file-20220309-20-mcpueg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/451131/original/file-20220309-20-mcpueg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=789&fit=crop&dpr=1 600w, https://images.theconversation.com/files/451131/original/file-20220309-20-mcpueg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=789&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/451131/original/file-20220309-20-mcpueg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=789&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/451131/original/file-20220309-20-mcpueg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=992&fit=crop&dpr=1 754w, https://images.theconversation.com/files/451131/original/file-20220309-20-mcpueg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=992&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/451131/original/file-20220309-20-mcpueg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=992&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">An ad promoting penicillin and its role in the war effort.</span>
<span class="attribution"><a class="source" href="https://www.nlm.nih.gov/exhibition/fromdnatobeer/exhibition-making-yellow-magic.html">Schenley Laboratories, Inc. advertisement, 1944</a></span>
</figcaption>
</figure>
<p>Almost exactly a year later, on March 14, 1942, doctors in Connecticut administered the antibiotic to a woman named <a href="https://www.nytimes.com/1999/06/09/us/anne-miller-90-first-patient-who-was-saved-by-penicillin.html">Anne Miller</a> who was deathly ill with streptococcal septicemia. She made a full recovery and became the first patient cured with penicillin. <a href="https://www.washingtonpost.com/history/2020/07/11/penicillin-coronavirus-florey-wwii-infection/">Mass production of penicillin</a> became a top priority of the U.S. War Department, second only to the Manhattan Project. It is widely believed that <a href="https://us.macmillan.com/books/9780805077780/the-mold-in-dr-floreys-coat">penicillin helped the Allies during World War II</a>, preventing wound infections and helping soldiers diagnosed with gonorrhea to return to the battlefield.</p>
<h2>The rosebush tale has been a thorn in their sides</h2>
<p>Albert Alexander has earned a place in history as the first known person to be treated with penicillin for a clinical condition. Almost as famous as his name is the purported cause of death: sepsis due to a scratch from rosebushes.</p>
<p>However, an alternative explanation was revealed in a <a href="https://www.ox.ac.uk/news/science-blog/penicillin-oxford-story">2010 interview with Eric Sidebottom</a>, a historian and author of “<a href="http://www.offoxpress.com/oxford-medicine-a-walk-through-nine-centuries.html">Oxford Medicine: A Walk Through Nine Centuries</a>.” He claimed that Alexander was injured when his police station was hit during a German bombing raid on Nov. 30, 1940. Shrapnel from this attack caused the facial lacerations that led to Alexander’s fatal blood poisoning, he said.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/451127/original/file-20220309-1729-ehbqqf.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="elderly woman holds up a black and white photo" src="https://images.theconversation.com/files/451127/original/file-20220309-1729-ehbqqf.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/451127/original/file-20220309-1729-ehbqqf.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=538&fit=crop&dpr=1 600w, https://images.theconversation.com/files/451127/original/file-20220309-1729-ehbqqf.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=538&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/451127/original/file-20220309-1729-ehbqqf.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=538&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/451127/original/file-20220309-1729-ehbqqf.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=676&fit=crop&dpr=1 754w, https://images.theconversation.com/files/451127/original/file-20220309-1729-ehbqqf.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=676&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/451127/original/file-20220309-1729-ehbqqf.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=676&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Sheila LeBlanc holding photo of her father, Albert Alexander, in 2012.</span>
<span class="attribution"><span class="source">Courtesy of Linda Willason</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>Alexander’s daughter, Sheila LeBlanc, who moved to California and became an artist, confirmed Sidebottom’s account in a <a href="https://www.pe.com/2012/11/02/redlands-local-artists-share-childhood-bond/">2012 interview</a> with a local newspaper. She also revealed the grim consequences Alexander’s death had on his family. Since they’d lived in a house provided by the village, for the village constable, his death forced them to move out. LeBlanc, who was seven at the time, and her older brother were sent to an orphanage, since their mother had to find work.</p>
<p>Michael Barrett, a professor of biochemical parasitology at the University of Glasgow, also spoke to LeBlanc about the cause of Alexander’s injury. <a href="https://mosaicscience.com/story/penicillin-first-patient-history-albert-alexander-AMR-DRI/">Writing in 2018, Barrett stated</a> that while LeBlanc recalled that the constable’s house did have a beautiful rose garden, <a href="http://www.fnrcnewbury.org.uk/biography.asp?BiogID=225&PersonID=2467">her father’s fatal cut</a> was sustained during the German blitz.</p>
<p>In February 2022, I contacted Alexander’s granddaughter, Linda Willason, who is also an artist in California, to help set the record straight. Willason validated the shrapnel account and suggested that the rosebush story was “a bit of wartime propaganda.” By downplaying bombing injuries, the government likely hoped to maintain the public’s stiff upper lip.</p>
<p>While the nature of Alexander’s injury may seem a trivial detail, correcting the historical record is important. Alexander died in the line of duty, and the apocryphal rosebush story obscures his honorable actions. His descendants are hopeful the true account of his injury will now eclipse the false one.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/450839/original/file-20220309-27-pxnrfz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="blue plaque with white text on brick wall" src="https://images.theconversation.com/files/450839/original/file-20220309-27-pxnrfz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/450839/original/file-20220309-27-pxnrfz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=413&fit=crop&dpr=1 600w, https://images.theconversation.com/files/450839/original/file-20220309-27-pxnrfz.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=413&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/450839/original/file-20220309-27-pxnrfz.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=413&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/450839/original/file-20220309-27-pxnrfz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=519&fit=crop&dpr=1 754w, https://images.theconversation.com/files/450839/original/file-20220309-27-pxnrfz.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=519&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/450839/original/file-20220309-27-pxnrfz.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=519&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A plaque dedicated in 2021 shares the real story of Alexander’s injury.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Albert_Alexander_plaque.jpg">Newbury Town Council/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>In 2021, <a href="https://www.bbc.com/news/uk-england-berkshire-57208267">a plaque commemorating Alexander</a> was installed in Newbury that reads: “On war support duty in Southampton on 30th November 1940, Albert was injured in an air raid. Contracting staphylococcal and streptococcal septicaemia, he was transferred to the Radcliffe Infirmary in Oxford, where he was selected for the first clinical application of penicillin. … His place in the history of antibiotics is secure.”</p>
<p>[<em>You’re smart and curious about the world. So are The Conversation’s authors and editors.</em> <a href="https://memberservices.theconversation.com/newsletters/?source=inline-youresmart">You can read us daily by subscribing to our newsletter</a>.]</p><img src="https://counter.theconversation.com/content/178463/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Bill Sullivan does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Albert Alexander was the first known person treated with penicillin. While his ultimately fatal case is well known in medical histories, the cause of his illness has been misattributed for decades.Bill Sullivan, Professor of Pharmacology & Toxicology, Indiana University School of MedicineLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1673542021-09-08T02:38:21Z2021-09-08T02:38:21ZThe world is desperate for new antibiotics, and New Zealand’s unique fungi are a source of promising compounds<figure><img src="https://images.theconversation.com/files/419899/original/file-20210907-12-1efw0kb.jpg?ixlib=rb-1.1.0&rect=11%2C0%2C1486%2C1122&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shara van der Pas</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>While we’re all rightly focused on the COVID-19 pandemic at the moment, the SARS-CoV-2 virus isn’t the only microbial threat we face. </p>
<p>Back in 2014, the World Health Organization (<a href="https://www.who.int/">WHO</a>) warned that within a decade, antibiotic-resistant bacteria could make routine surgery, organ transplantation and cancer treatment life-threateningly risky — and spell the <a href="https://abcnews.go.com/blogs/health/2012/03/16/antibiotic-resistance-could-bring-end-of-modern-medicine">end of modern medicine</a> as we know it.</p>
<figure class="align-right ">
<img alt="Petri dishes with fungi growing on them" src="https://images.theconversation.com/files/419905/original/file-20210907-18-1i6y2tn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/419905/original/file-20210907-18-1i6y2tn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=800&fit=crop&dpr=1 600w, https://images.theconversation.com/files/419905/original/file-20210907-18-1i6y2tn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=800&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/419905/original/file-20210907-18-1i6y2tn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=800&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/419905/original/file-20210907-18-1i6y2tn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1005&fit=crop&dpr=1 754w, https://images.theconversation.com/files/419905/original/file-20210907-18-1i6y2tn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1005&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/419905/original/file-20210907-18-1i6y2tn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1005&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Fungi produce compounds to fight bacteria.</span>
<span class="attribution"><span class="source">Manaaki Whenua</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>Antibiotics are a cornerstone of modern medicine, used to treat infections and to protect vulnerable patients undergoing surgery or chemotherapy. The world desperately needs new antibiotics and COVID-19 has only exacerbated the problem.</p>
<p>In our search for new antibiotics, we have focused on fungi, especially those found only in Aotearoa New Zealand. Our latest <a href="https://www.frontiersin.org/articles/10.3389/fmicb.2021.739995/full">research</a> describes the discovery of fungal compounds able to kill Mycobacteria, a family of slow-growing bacteria that includes another important global airborne killer — <em>Mycobacterium tuberculosis</em> — which causes the lung disease tuberculosis and kills thousands of people around the world each day.</p>
<p>While most people in Aotearoa know me as the “pink-haired COVID lady”, for the past six years my lab has been hunting for compounds that could make good antibiotics. We’ve focused on fungi from the International Collection of Microorganisms from Plants (<a href="https://www.landcareresearch.co.nz/tools-and-resources/collections/icmp-culture-collection/">ICMP</a>), cared for by the Crown Research Institute <a href="https://www.landcareresearch.co.nz/">Manaaki Whenua</a> and our collaborator <a href="https://www.landcareresearch.co.nz/about-us/our-people/bevan-weir">Bevan Weir</a>. </p>
<p>Our latest findings follow <a href="https://www.mdpi.com/1420-3049/26/4/1094">earlier research</a> which revealed a fungal compound with some activity against the hospital superbug methicillin-resistant <em>Staphylococcus aureus</em>, better known as MRSA. </p>
<h2>Why fungi?</h2>
<p>One of the earliest antibiotics ever discovered, penicillin, originally came from a fungus called <em>Penicillium rubens</em>. With more than 10,000 fungi in the ICMP database, we think this may be a treasure trove of potential new antibiotics.</p>
<p>For our latest <a href="https://www.frontiersin.org/articles/10.3389/fmicb.2021.739995/full">study</a>, we tested 36 fungi collected between 1961 and 2016 from locations right across Aotearoa, including the Chatham Islands. Our first exciting finding is that nine of the fungi are not known species, suggesting they may well be unique to Aotearoa. </p>
<figure class="align-right ">
<img alt="Scientist looking down a microscope" src="https://images.theconversation.com/files/419907/original/file-20210907-23-zdpuq6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/419907/original/file-20210907-23-zdpuq6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/419907/original/file-20210907-23-zdpuq6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/419907/original/file-20210907-23-zdpuq6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/419907/original/file-20210907-23-zdpuq6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/419907/original/file-20210907-23-zdpuq6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/419907/original/file-20210907-23-zdpuq6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Bevan Weir explores microorganisms derived from plants.</span>
<span class="attribution"><span class="source">Manaaki Whenua</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>Aotearoa is well known for its iconic animal and plant species that aren’t found anywhere else in the world. Our fungi will be no different. And if they are unique, they may have come up with unique compounds able to kill bacteria. </p>
<p>Our second major finding is that 35 of the 36 fungi we tested had some form of antibacterial activity against Mycobacteria. In fact, when we first started doing this work, we thought we must have made a mistake. We’d never had anything like that kind of success rate when screening fungi against other superbugs. </p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/how-we-discovered-a-hidden-world-of-fungi-inside-the-worlds-biggest-seed-bank-156051">How we discovered a hidden world of fungi inside the world’s biggest seed bank</a>
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<p>Taking a deeper dive into the chemistry of those fungal compounds, we found the majority are fatty acids which won’t make good antibiotics. But we did find several fungi, including two of our unknown species, whose antibacterial activity wasn’t due to fatty acids. </p>
<p>We’re currently working to identify these compounds, with our collaborators <a href="https://unidirectory.auckland.ac.nz/profile/mcad006">Melissa Cadelis</a> and <a href="https://unidirectory.auckland.ac.nz/profile/b-copp">Brent Copp</a>.</p>
<h2>Long road to discovery</h2>
<p>Physicist Jim Al-Khalili once said that most scientific progress is a “messy, complex and slow process”. Take the COVID-19 vaccines as a good example. While we’ve watched numerous vaccines come through clinical trials successfully and quickly, they are based on <a href="https://www.nature.com/articles/s41578-021-00358-0">decades of scientific study</a> of mRNA and lipid nanoparticles. </p>
<p>My lab’s search for antibiotics has its roots in work we did over a decade ago, making tools to make <a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0010777">Mycobacteria glow in the dark</a>. Because these bacteria grow so slowly, it can take weeks to months for them to form colonies on a petri dish. </p>
<p>But they glow only when they are alive, and this technique allows us to measure the amount of light they produce instead of waiting for them to grow. This massively speeds up the antibiotic discovery process. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/new-technology-can-create-treatment-against-drug-resistant-bacteria-in-under-a-week-and-adapt-to-antibiotic-resistance-163710">New technology can create treatment against drug-resistant bacteria in under a week and adapt to antibiotic resistance</a>
</strong>
</em>
</p>
<hr>
<p>I started thinking about fungi as a potential source of new antibacterial compounds when Manaaki Whenua’s fungi expert Peter Buchanan told me about the collection. After a few years of rejected funding applications, we finally got a small grant-in-aid from <a href="https://curekids.org.nz/">Cure Kids</a> to get the project started in 2015. </p>
<p>One of their ambassadors, <a href="https://curekids.org.nz/ambassadors/eva/">Eva</a>, has battled superbug infections her whole life. Meeting Eva changed my relationship with my work and inspired me to do all I can to find new antibiotics. </p>
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<figcaption><span class="caption">Eva is a Cure Kids ambassador who lives with MRSA and was born with a hole in her diaphragm.</span></figcaption>
</figure>
<p>We’ve still got a way to go before we have any compounds that might be suitable for further development as antibiotics. We also know that many compounds fail as they move through the pipeline that takes them from the lab to clinical trials in humans. </p>
<p>That’s why my lab will keep working its way through the fungal collection for as long as we can afford to. There are thousands more fungi to screen and hopefully many more unique compounds with antibiotic potential to discover.</p><img src="https://counter.theconversation.com/content/167354/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Siouxsie Wiles receives funding from Cure Kids and NZ Carbon Farming. This work was previously supported by grants-in-aid from the Maurice Wilkins Centre for Molecular Biodiscovery and the University of Auckland.</span></em></p>Penicillin originally came from a fungus, and with thousands of fungi to explore, Aotearoa New Zealand has a potential treasure trove of bacteria-killing compounds.Siouxsie Wiles, Associate Professor in Microbiology and Infectious Diseases, University of Auckland, Waipapa Taumata RauLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1209902019-08-08T09:45:30Z2019-08-08T09:45:30ZMyth about how science progresses is built on a misreading of the story of penicillin<figure><img src="https://images.theconversation.com/files/286920/original/file-20190805-36363-ij0snc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/penicillium-ascomycetous-fungi-major-importance-natural-747671938?src=z6hOzyS7QtRbZrdUIJLMVQ-1-16&studio=1">Rattiya Thongdumhyu/Shutterstock</a></span></figcaption></figure><p>Many professions have creation myths about much-revered pioneers. For nursing, it is <a href="http://www.bbc.co.uk/history/british/victorians/nightingale_01.shtml">Florence Nightingale</a> in Scutari, flitting between beds bearing her lamp. For engineers, it is <a href="http://www.bbc.co.uk/history/historic_figures/brunel_kingdom_isambard.shtml">Isambard Kingdom Brunel</a>, driving railway lines across the countryside and building ships. These myths often tell us more about how professions want to be seen than about the historic events on which they are based.</p>
<p>One of the myths in medical science is the discovery of penicillin. It has been retold to generations of school children: <a href="https://www.nobelprize.org/prizes/medicine/1945/fleming/biographical/">Alexander Fleming</a> came back from his holidays in 1928 to his laboratory at St Mary’s Hospital in London and looked at some petri dishes before throwing them away. On one of the dishes he sees a mould growing, with a clearing around it where the bacteria had been killed. A eureka moment allows him to deduce that the fungus is releasing a molecule that kills the bacteria. </p>
<p>The action then moves to Oxford where <a href="http://adb.anu.edu.au/biography/florey-howard-walter-10206">Howard Florey</a> and <a href="https://www.britannica.com/biography/Ernst-Boris-Chain">Ernst Chain</a> discover how to isolate the molecule, now called penicillin. They realise the importance of the drug for the war effort, and with the help of American companies, large amounts of penicillin arrive just in time to treat wounded allied soldiers during World War II. The curtain call is taken by Fleming, Chain and Florey when they win a <a href="https://www.nobelprize.org/prizes/medicine/1945/summary/">Nobel Prize</a> in 1945.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/286922/original/file-20190805-36395-qdpmix.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/286922/original/file-20190805-36395-qdpmix.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=392&fit=crop&dpr=1 600w, https://images.theconversation.com/files/286922/original/file-20190805-36395-qdpmix.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=392&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/286922/original/file-20190805-36395-qdpmix.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=392&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/286922/original/file-20190805-36395-qdpmix.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=493&fit=crop&dpr=1 754w, https://images.theconversation.com/files/286922/original/file-20190805-36395-qdpmix.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=493&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/286922/original/file-20190805-36395-qdpmix.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=493&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Fleming receiving the Nobel Prize from King Gustaf V of Sweden in 1945.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/w/index.php?curid=6230654">Wikimedia Commons</a></span>
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<p>This is a very satisfying story. It includes the serendipity of a contaminated culture dish (the <a href="https://www.londonremembers.com/memorials/fountains-abbey-public-house">Fountains Abbey pub</a> in nearby Praed Street makes unlikely claims that the mould came from their beer, tying the discovery of penicillin into British culture). It involves a moment of effortless brilliance, with Fleming seeing the implications of the clearing. It describes research working out in a predictable and rapid manner; once Fleming saw the dish, it was just a matter of time before the wonder drug started saving lives.</p>
<h2>Not a priority</h2>
<p>Much of this is wrong. The story of Fleming seeing the clearing <a href="https://www.goodreads.com/book/show/406931.The_Mold_in_Dr_Florey_s_Coat">first appeared in 1944</a>. It is not supported by the notes he wrote at the time and is difficult to reconcile with the growth of <em>Penicillium</em> and <em>Staphylococcus aureus</em>, nor by how penicillin works. It appeared at a time of great tension and competition between St Mary’s and Oxford scientists.</p>
<p>What is often missed is the time and effort it took to get from Fleming’s initial discovery to production of the drug. In part this is because it was not a priority for Fleming. It was not obvious that penicillin was of any interest, when results were presented at scientific meetings, they were often met with indifference.</p>
<p>It was very hard to isolate the active ingredient of the “mould juice” – several scientists tried and failed. It needed the biochemical skills and inventiveness of the Oxford scientists to <a href="https://www.goodreads.com/book/show/406931.The_Mold_in_Dr_Florey_s_Coat">solve this problem</a>.</p>
<p>The Oxford group made superhuman efforts to make enough penicillin to treat patients, initially growing the mould in bedpans. </p>
<p>The first person treated was a policeman, <a href="https://en.wikipedia.org/wiki/Albert_Alexander_(police_officer)">Albert Alexander</a>, who had an uncontrolled bacterial infection following a rose scratch. He responded dramatically to penicillin, seeming to recover. But ten days later, he relapsed, and despite having recycled penicillin from his urine, supplies ran out and he died of his infection.</p>
<p>The final step was the scaling up and industrialisation. This stage is often forgotten. UK companies did not have the capacity, resources or vision to manufacture penicillin. Florey turned to US industries who developed new ways to isolate penicillin. This was not trivial, and by 1945 US companies were making <a href="https://www.acs.org/content/acs/en/education/whatischemistry/landmarks/flemingpenicillin.html">6.8 trillion units</a> – slightly more than 4,000kg of the drug a year.</p>
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<img alt="" src="https://images.theconversation.com/files/286924/original/file-20190805-36367-11fp6ri.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/286924/original/file-20190805-36367-11fp6ri.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=486&fit=crop&dpr=1 600w, https://images.theconversation.com/files/286924/original/file-20190805-36367-11fp6ri.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=486&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/286924/original/file-20190805-36367-11fp6ri.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=486&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/286924/original/file-20190805-36367-11fp6ri.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=611&fit=crop&dpr=1 754w, https://images.theconversation.com/files/286924/original/file-20190805-36367-11fp6ri.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=611&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/286924/original/file-20190805-36367-11fp6ri.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=611&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">By 1945, penicillin was finally being mass produced.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/w/index.php?curid=1819576">Wikimedia Commons</a></span>
</figcaption>
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<h2>Long and winding road</h2>
<p>It took 16 years from initial observation to useful production of penicillin, and it would have been much longer without the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3673487/">impetus given by the war</a>. Exploitation of scientific results takes time, persistence and different skills.</p>
<p>But is the final part of the story true? Did penicillin help win the war? It certainly saved thousands of soldiers from dying of gangrene and sepsis. But its greatest contribution to the war effort may have been the treatment of gonorrhoea, helping keep the army at full strength. </p>
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<p>
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<strong>
Read more:
<a href="https://theconversation.com/how-boris-johnson-draws-on-the-past-to-rule-in-the-present-with-a-little-help-from-myth-120863">How Boris Johnson draws on the past to rule in the present – with a little help from myth</a>
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</em>
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<p>During the invasion of Sicily, when penicillin was still in short supply, some argued that it should be reserved for wounded soldiers, rather than to relieve “scallywags” of the consequences of their own indiscretions. This was <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1599833/">overruled by Churchill</a>, who said it was to be used to obtain the “best military advantage”.</p>
<p>What are the dangers of the penicillin myth? I suggest that it emphasises a model of scientific discovery that is effortless and dependent on individual genius. That is not fair on Fleming, he was prepared for his discovery by years of hard work, and it involved a series of difficult experiments.</p>
<p>It also suggests that, once the discovery is made, science proceeds down a predictable path to exploitation. This is not the case, the reason it took time to develop penicillin is because it was a hard thing to do and its potential was not obvious.</p>
<p>Finally, the myth concentrates on individuals, in particular Fleming. While his contribution was vital, that of Florey and Chain was equally important. The contribution of <a href="https://www.goodreads.com/book/show/406931.The_Mold_in_Dr_Florey_s_Coat">Norman Heatley</a> was key to the biochemical isolation. Countless other scientists and industrialists were involved. <a href="https://www.encyclopedia.com/people/history/historians-miscellaneous-biographies/edward-mellanby">Edward Mellanby</a>, the secretary of the Medical Research Council, saw the potential and sorted much of the funding. Patients, doctors, nurses and technicians, including the “<a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)30957-1/fulltext">penicillin girls</a>” who prepared the penicillin, all played their role. Science is a shared enterprise.</p>
<p>Myths are important, but sometimes it is useful to look behind them to understand how science really works.</p><img src="https://counter.theconversation.com/content/120990/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Andrew George is Chair of Imperial College Health Partners, he is a Non-Executive Director of the Health Research Authority.</span></em></p>Science is rarely about an individual genius saving the day.Andrew George, Emeritus Professor, Brunel University LondonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1158362019-06-05T12:44:29Z2019-06-05T12:44:29ZAntibiotic resistance is not new – it existed long before people used drugs to kill bacteria<figure><img src="https://images.theconversation.com/files/277728/original/file-20190603-69083-1udxh77.jpg?ixlib=rb-1.1.0&rect=7%2C0%2C5274%2C3315&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Antibiotic resistance can spread between microbes within hours.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/antibiotic-resistant-virus-deadly-mutated-viral-1061567048?src=e5Gb-FbQa_h3iFLWbEPxjA-1-0">Lightspring/Shutterstock.com</a></span></figcaption></figure><p>Imagine a world where your odds of surviving minor surgery were <a href="https://www.gov.uk/government/publications/english-surveillance-programme-antimicrobial-utilisation-and-resistance-espaur-report">one to three</a>. A world in which a visit to the dentist could spell disaster. This is the world into which your great-grandmother was born. And if humanity loses the fight against antibiotic resistance, this is a world your <a href="https://doi.org/10.1016/j.cmi.2015.12.002">grandchildren may well end up revisiting</a>. </p>
<p>Antibiotics changed the world in more ways than one. They made surgery routine and childbirth safer. Intensive farming was born. For decades, antibiotics have effectively killed or stopped the growth of disease-causing bacteria. Yet it was always clear that this would be a rough fight. Bacteria breed fast, and that means that they adapt rapidly. The emergence of antibiotic resistance was <a href="https://doi.org/10.1289/ehp.117-a244">predicted by none other than Sir Alexander Fleming</a>, the discoverer of penicillin, less than a year after the first batch of penicillin was mass produced. </p>
<p>Yet, contrary to popular belief, antibiotic resistance did not evolve recently, or in response to our use and misuse of antibiotics in humans and animals. Antibiotic resistance first evolved millions of years ago, and in the most mundane of places.</p>
<p>I am a bioinformatician, and <a href="https://erilllab.umbc.edu/">my lab</a> studies the evolution of bacterial genomes. With <a href="https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance">antibiotic resistance becoming a major threat</a>, I’m trying to figure out how resistance to antibiotics emerges and spreads among bacterial populations.</p>
<h2>A billion-years-old arms race</h2>
<p>Most antibiotics are naturally produced by bacteria living in soil. They produce these deadly chemical compounds to fend off competing species. Yet, in the long game that is evolution, competing species are unlikely to sit idly by. Any mutant capable of tolerating a minimal quantity of the antibiotic will have a survival advantage and will be selected for – over generations this will produce organisms that are highly resistant. </p>
<p>So it’s a foregone conclusion that antibiotic resistance, for any antibiotic researchers might ever discover, is likely already out there. Yet people keep talking about the evolution of antibiotic resistance as a <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159373/">recent phenomenon</a>. Why?</p>
<p>Resistance can and does evolve when bacteria are persistently exposed to a new antibiotic they have never encountered. Let’s call this the old-fashioned evolutionary road. Second, when bacteria are exposed to a novel antibiotic and are in contact with bacteria already resistant to this antibiotic, it is just a matter of time before they <a href="https://doi.org/10.1126/science.aav6390">get cozy and trade genes</a>. And, importantly, once genes have been packaged for trading, they become easier and easier to share. Bacteria then meet other bacteria, which meet more bacteria, until one of them eventually meets you.</p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/plVk4NVIUh8?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Bacteria can evolve resistance to high levels of antibiotics in just days.</span></figcaption>
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<h2>The rise and fall of sulfa drugs</h2>
<p>For all their might, antibiotics are not the only substances capable of effectively killing bacteria (without killing us). A decade before the mass production of penicillin, sulfonamide drugs became the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC162528/">first commercial antibacterial agent</a>. Sulfa drugs act by blocking an enzyme – called DHPS – that is essential for bacteria to grow and multiply. </p>
<p>Sulfa drugs are not antibiotics. No known organism produces them. They are chemotherapeutic agents synthesized by humans. No natural producer means no billion-year-old arms race and no pool of ancient resistance genes. We would expect bacteria to evolve resistance to sulfa drugs via the good old-fashioned way. And they did. </p>
<p>Just a few years after their commercial introduction, the first cases of resistance to sulfa drugs <a href="https://mh.bmj.com/content/38/1/55.long">were reported</a>. Mutations to the bacterial DHPS enzyme made sulfa drugs ineffective. Then penicillin and the antibiotic era came about. Sulfa drugs were relegated to a <a href="https://linkinghub.elsevier.com/retrieve/pii/S1368-7646(00)90146-8">secondary role</a> in medicine, but they gained popularity as cheap antimicrobials in animal husbandry. By the 1980s resistance to sulfa drugs was rampant and worldwide. What had happened? </p>
<h2>At odds with resistance</h2>
<p>To answer this question our research team took sequences of sulfa drug resistance genes from disease-causing bacteria and <a href="https://doi.org/10.3389/fmicb.2018.03332">compared them</a> to millions of “normal” versions of the DHPS enzyme in nonpathogenic bacteria.</p>
<p>The team identified two large groups of bacteria that had DHPS enzymes resistant to sulfa drugs. By studying their DNA sequences, we were able to show that these resistant DHPS enzymes had been present in these two groups of bacteria for at least 500 million years. Yet sulfa drugs were first synthesized in the 1910s. How could resistance be around 500 million years ago? And how did these resistance genes find their way into the disease-causing bacteria plaguing hospitals worldwide? </p>
<p>The clues left in gene sequences are too fuzzy to conclusively answer the latter, but we can certainly speculate. The bacteria we identified as harboring these ancient sulfa drug resistance genes are all soil and freshwater bacteria that thrive under the well-irrigated subsoil of farms. And farmers have been adding huge amounts of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC162528/">sulfa drugs to animal feed</a> for the past 50 years. </p>
<p>The sublethal concentrations of sulfa drugs in the soil are the perfect setting for resistance genes to be transferred from these ancient resistant bacterial populations to other bacteria. All it takes is for one lucky bacterium to meet one of these ancient resistant ones in the subsoil. They trade some genes, one bacterium to the next, and resistance spreads until a newly minted resistant bacterium eventually makes it to the groundwater supply you drink from. You do the math.</p>
<h2>Nothing new under the sun</h2>
<p>As for why sulfa drug resistance genes would be around 500 million years ago, there are two plausible explanations. On the one hand, it could be that 500 million years ago there was a bacterium that synthesized sulfa drugs, which would explain the evolution of resistance. However, the lack of remnants from such a biosynthetic pathway makes this unlikely.</p>
<p>On the other hand, resistant bacteria may have been around just by chance. The argument here is that there are so many bacteria, and such diversity, that chances are that some of them are going to be resistant to anything scientists come up with. This is a sobering thought. </p>
<p>Then again, this is already the baseline for antibiotics. Like climate change, antibiotic resistance is one of those problems that always seem to be a couple decades away. And it may well be. A turning point for me in the climate change debate was a decade-old opinion piece in New Scientist. It stated that we should make every possible effort to prevent climate change, especially in the unlikely case that it was not caused by man, because that would mean that all we can do is palliate a natural phenomenon. </p>
<p>Our research points in the same direction. If resistance is already out there, drug development can offer only temporary relief. The challenge then is not to quell resistance, but to avoid its spread. It is a big challenge, but not an insurmountable one. Not feeding wonder drugs to pigs would do nicely, for starters.</p><img src="https://counter.theconversation.com/content/115836/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ivan Erill does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Resistance to antibiotics is not a new trait, and it is impossible to prevent. But it is possible to avoid its spread.Ivan Erill, Associate Professor of Biological Sciences, University of Maryland, Baltimore CountyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1126872019-04-25T20:12:48Z2019-04-25T20:12:48ZThink you’re allergic to penicillin? There’s a good chance you’re wrong<figure><img src="https://images.theconversation.com/files/268704/original/file-20190411-2914-mksw66.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A rash people assume is a reaction to penicillin may not be related to the drug at all.</span> <span class="attribution"><span class="source">From shutterstock.com</span></span></figcaption></figure><p>Are you allergic to penicillin? Perhaps you have a friend or relative who is? With about <a href="https://www.mja.com.au/system/files/issues/208_11/10.5694mja17.00487.pdf">one in ten</a> people reporting a penicillin allergy, that’s not altogether surprising.</p>
<p>Penicillin is the <a href="https://www.bmj.com/content/358/bmj.j3402">most commonly reported</a> drug allergy. But the key word here is “reported”. Only about 20% of this 10% have a true penicillin allergy – so the figure would be one in 50 rather than one in ten.</p>
<p>People may experience symptoms they think are a result of taking penicillin, but are actually unrelated. If these symptoms are not investigated, they continue with the belief that they should steer clear of penicillin.</p>
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Read more:
<a href="https://theconversation.com/weekly-dose-penicillin-the-mould-that-saves-millions-of-lives-63770">Weekly Dose: penicillin, the mould that saves millions of lives</a>
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<p>This can become a problem if a person is sick and needs to be treated with penicillin. Penicillin and related antibiotics are the most common group of drugs used to treat a <a href="https://www.safetyandquality.gov.au/publications/second-australian-report-on-antimicrobial-use-and-resistance-in-human-health/">broad range of infections</a>, from chest or throat, to urinary tract, to skin and soft tissue infections.</p>
<p>The overestimation of penicillin allergies is also not ideal because it means people are being treated with a broader range of antibiotics than necessary, which contributes to the problem of antibiotic resistance.</p>
<h2>Yes, penicillin comes from mould</h2>
<p>To understand more about why so many people think they’re allergic to penicillin, we need to look at a brief history of the drug.</p>
<p>Penicillin (benzylpenicillin or Penicillin G) was <a href="https://wwwnc.cdc.gov/eid/article/23/5/16-1556_article">first discovered</a> in 1928 and first used in 1941.</p>
<p>It was grown from a mould, as it is today. The liquid nutrient broth the mould grew in was drained, and the penicillin purified from it.</p>
<p>In the 1930s and 40s, and even through the 1960s and 70s, purification techniques were not as efficient as they are today. So, many early allergic reactions are thought to be due to impurities in the early penicillin products – especially injections.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/268702/original/file-20190411-2935-162etbc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/268702/original/file-20190411-2935-162etbc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/268702/original/file-20190411-2935-162etbc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/268702/original/file-20190411-2935-162etbc.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/268702/original/file-20190411-2935-162etbc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/268702/original/file-20190411-2935-162etbc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/268702/original/file-20190411-2935-162etbc.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Penicillin is now more versatile and can kill a wider range of bacteria than in its earlier days.</span>
<span class="attribution"><span class="source">From shutterstock.com</span></span>
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</figure>
<p>Penicillin and the range of antibiotic compounds that followed it revolutionised how we treat bacterial infections.</p>
<p>This led to widespread, and sometimes inappropriate, use of these medicines. Antibiotics <a href="https://www.healthymepa.com/2017/02/21/do-you-need-antibiotics/">do not work against viruses</a>, but are sometimes prescribed for bacterial infections that occur while people have viral infections such as glandular fever.</p>
<p>We know using penicillin while a person has glandular fever can cause a rash that looks like penicillin allergy but is not related.</p>
<p>People may report symptoms to their health professionals that seem like a reaction to penicillin. Perhaps these symptoms are not fully investigated because it takes time and can be expensive – they’re just put down to the common penicillin allergy.</p>
<p>Further, some people perceive other side effects of a penicillin antibiotic such as nausea or diarrhoea as an allergy, when these are not, in fact, allergy symptoms.</p>
<p>From this point, the penicillin family will not be used to treat these patients. </p>
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Read more:
<a href="https://theconversation.com/we-know-why-bacteria-become-resistant-to-antibiotics-but-how-does-this-actually-happen-59891">We know _why_ bacteria become resistant to antibiotics, but _how_ does this actually happen?</a>
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<h2>The problem of antibiotic resistance</h2>
<p>An allergy to penicillin can also limit the use of some other antibiotics <a href="https://jamanetwork.com/journals/jama/article-abstract/2720732">which may cross-react</a> with the allergy. </p>
<p>Cross reaction occurs when the chemical structure of another antibiotic is so similar to the structure of penicillin that the immune system gets confused and recognises it as the same thing.</p>
<p>To avoid this, doctors need to look to antibiotics from other medication classes when prescribing patients with a documented penicillin allergy.</p>
<p>But we need to be careful when drawing on a wider range of antibiotics. This is because the more bacteria are exposed to antibiotics, the more likely they are to develop resistance to these antibiotics.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/268705/original/file-20190411-2927-nshdsg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/268705/original/file-20190411-2927-nshdsg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/268705/original/file-20190411-2927-nshdsg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/268705/original/file-20190411-2927-nshdsg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/268705/original/file-20190411-2927-nshdsg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/268705/original/file-20190411-2927-nshdsg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/268705/original/file-20190411-2927-nshdsg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">The range of penicillins we have today came from experimenting with the chemistry of the original penicillin molecule and changing its properties.</span>
<span class="attribution"><span class="source">From shutterstock.com</span></span>
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</figure>
<p>To address the growing problem of antibiotic resistance, we now try to restrict antibiotics as much as possible to the lowest level one that will kill the specific bacteria.</p>
<p>We don’t kill tiny ants in our gardens with a sledgehammer, so likewise, we use a narrow-spectrum antibiotic wherever possible to keep the broad-spectrum antibiotics for severe and complex infections. </p>
<p>The penicillin family contains both narrow and broad-spectrum antibiotics. Ruling out this family and its “cousins” when we don’t need to can limit the choice of antibiotics and increase the chance of making other antibiotics less useful. </p>
<h2>Can I get tested?</h2>
<p>Studies show penicillin allergy <a href="https://newsnetwork.mayoclinic.org/discussion/mayo-clinic-q-and-a-how-could-my-penicillin-allergy-go-away/">reduces over time</a>. So even if you did have a true penicillin allergy, it may have gone away over several years.</p>
<p>Under the guidance of your doctor, it is possible to be tested to see if you’re allergic – or still allergic – to penicillin.</p>
<p>A skin “scratch” test involves injecting a small amount of penicillin and monitoring for a reaction. Rescue medications will be on hand in case you do have a severe reaction. Your GP will probably refer you to an allergy specialist to get this done.</p>
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Read more:
<a href="https://theconversation.com/common-skin-rashes-and-what-to-do-about-them-91518">Common skin rashes and what to do about them</a>
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<p>If you have been told you’re allergic, you should first try to find out when the reaction occurred and what happened in as much detail as possible. </p>
<p>Let your GP know all this information and he or she can then decide whether a skin test might be appropriate.</p>
<p>Do not try a test dose at home – the risk of a life-threatening reaction is not worth it.</p>
<p>And if you believe you are allergic to penicillin, the most important thing to do is tell each health professional (doctor, pharmacist, nurse, dentist, etc.) you come into contact with.</p><img src="https://counter.theconversation.com/content/112687/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Greg Kyle does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>About 10% of people believe they’re allergic to penicillin. Only about 2% actually are.Greg Kyle, Professor of Pharmacy, Queensland University of TechnologyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1096582019-02-13T02:06:38Z2019-02-13T02:06:38ZSyphilis is making a come-back, and causing some unusual health problems<figure><img src="https://images.theconversation.com/files/258451/original/file-20190212-174883-g9w2gc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Syphilis can cause vision loss, and it's on the rise. </span> <span class="attribution"><span class="source">from www.shutterstock.com</span></span></figcaption></figure><p>Syphilis is a sexually transmissible infectious disease that has plagued humankind for centuries. Today, syphilis is diagnosed rapidly by a simple blood test, and easily treated with an inexpensive antibiotic. However, the disease may masquerade as other medical conditions, confusing even health care professionals. A delay in diagnosis and treatment may have serious medical consequences.</p>
<p>There’s ongoing debate about the origin of syphilis, but the disease is <a href="https://jmvh.org/article/syphilis-its-early-history-and-treatment-until-penicillin-and-the-debate-on-its-origins/">well described in the medical literature</a> from the Middle Ages. The name “syphilis” was coined in 1530 by an Italian physician. Dr. Girolamo Fracastoro wrote a poem describing features of the illness in a fictional shepherd named Syphilus, who had blasphemed against the Sun-God and was punished with a severe case of the disease.</p>
<p>Since this time, syphilis has claimed many lives and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3956094/">influenced civilisation</a> in <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1048214/">diverse ways</a>. </p>
<p>Syphilis has afflicted heads of state, whose nations have suffered from the consequences of their diminished mental health. King Henry VIII of England and Tsar Ivan IV Vasilievici of Russia (“Ivan the Terrible”) are examples. Careers of internationally influential artists – such as Ludwig van Beethoven, Oscar Wilde and Scott Joplin – ended prematurely due to syphilis. </p>
<p>Public outrage over the highly unethical <a href="https://www.history.com/news/the-infamous-40-year-tuskegee-study">Tuskegee study</a> and Guatemalan experiments on people with untreated syphilis have helped to shape present day human research regulations.</p>
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Read more:
<a href="https://theconversation.com/three-charts-on-the-state-of-stis-and-blood-borne-viruses-in-australia-86298">Three charts on the state of STIs and blood-borne viruses in Australia</a>
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<h2>Cause and effect</h2>
<p><a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)32411-4/fulltext">Syphilis is caused by</a> a spiral shaped bacterium called Treponema pallidum. Although the <a href="https://www.nature.com/articles/nrdp201773">bacteria multiply slowly</a>, they are easily passed between sexual partners via the skin or mucous membranes. </p>
<p>A small ulcer is the typical “first stage” of syphilis. The ulcer does not appear until several weeks after the sexual encounter, and it is painless, short-lived and heals without a trace. So it may go unnoticed, especially if it occurs in an inconspicuous place, inside vaginal or rectal passages, or in the mouth.</p>
<p>The second stage of syphilis is characterised by unusual skin and mucous membrane rashes that improve without treatment over weeks to months. The disease then enters a period called the latent stage that lasts for years, during which a person has no symptoms, but continues to be infected.</p>
<p>Finally, in the tertiary stage, syphilis becomes <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)32411-4/fulltext">extremely destructive</a>. Large inflammatory growths that occur anywhere in the body may seriously damage tissues. There may be aneurysms, heart disease, dementia and paralysis. </p>
<p><a href="https://www.nature.com/articles/nrdp201773">Syphilis can also be passed</a> from a pregnant woman to her unborn child, resulting in a serious illness and sometimes loss of the baby.</p>
<p>Throughout the course of syphilis, the nervous system and senses may become affected, <a href="https://www.nature.com/articles/s41598-018-30559-7">causing unusual health problems</a>. This includes inflammation inside the eye, called uveitis. Syphilitic uveitis causes vision loss in about two-thirds of people who develop it, and may lead on to other eye conditions, such as cataract, glaucoma, retinal scarring and retinal detachment.</p>
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<a href="https://images.theconversation.com/files/258626/original/file-20190213-90491-du67d2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/258626/original/file-20190213-90491-du67d2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/258626/original/file-20190213-90491-du67d2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=409&fit=crop&dpr=1 600w, https://images.theconversation.com/files/258626/original/file-20190213-90491-du67d2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=409&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/258626/original/file-20190213-90491-du67d2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=409&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/258626/original/file-20190213-90491-du67d2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=513&fit=crop&dpr=1 754w, https://images.theconversation.com/files/258626/original/file-20190213-90491-du67d2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=513&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/258626/original/file-20190213-90491-du67d2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=513&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Oscar Wilde is one of many well-known people throughout history who suffered from syphilis.</span>
<span class="attribution"><span class="source">from www.shutterstock.com</span></span>
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<h2>Treatment</h2>
<p>Introduction of penicillin into medical practice in the 1940s provided an opportunity to eradicate syphilis, as Treponema is highly sensitive to this antibiotic. In countries where testing and antibiotics were readily available, rates of syphilis dropped to extremely low levels during the 20th century. </p>
<p>In Australia in 2010, there were just <a href="https://kirby.unsw.edu.au/report/hiv-viral-hepatitis-and-sexually-transmissible-infections-australia-annual-surveillance">five reported new infections</a> per 100,000 people. Hope was high that the same might be achieved in low income, developing nations.</p>
<p>Unexpectedly, however, rates of syphilis are climbing in high income countries across the globe. <a href="https://kirby.unsw.edu.au/report/hiv-viral-hepatitis-and-sexually-transmissible-infections-australia-annual-surveillance">Latest figures</a> from the Kirby Institute indicate an increase by over 250% between 2010 and 2017, affecting both Australian men and women. </p>
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354565/">Many factors are responsible</a>. Aware of the highly effective drugs for HIV infection, people are less concerned about safe sex. Other factors that promote spread of the Treponema bacteria are high levels of travel and new drugs for sexual dysfunction. There is also a relationship between HIV infection and syphilis: having one infection increases the risk of catching the other. </p>
<p>This creates a challenging situation for health care professionals, who are suddenly encountering patients with a disease they did not focus on during their training. Add to this that syphilis may masquerade as a wide range of other medical conditions as it moves past the first stage. It is actually referred to in clinical textbooks as the Great Imitator or the Great Mimicker.</p>
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Read more:
<a href="https://theconversation.com/stigma-and-lack-of-awareness-stop-young-people-testing-for-sexually-transmitted-infections-80265">Stigma and lack of awareness stop young people testing for sexually transmitted infections</a>
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<h2>Ocular syphilis</h2>
<p>As ophthalmologists we have noticed an increase in cases of syphilitic uveitis. A delay in starting penicillin can result in permanent vision loss. In one <a href="https://www.nature.com/articles/s41598-018-30559-7">very large study conducted in Brazil</a>, it took about three months to recognise syphilis as the cause of uveitis, and half of people in the study did not fully recover their vision despite taking antibiotics.</p>
<p>Ophthalmologists who specialise in uveitis identify the lack of medical suspicion for the diagnosis of syphilis as an <a href="https://bjo.bmj.com/content/early/2019/01/30/bjophthalmol-2018-313207">important reason for a delay</a> to starting treatment.</p>
<h2>Prevention</h2>
<p>There is no vaccine for syphilis, and a person may catch it <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)32411-4/fulltext">more than once</a>. But there are ways to avoid the health problems caused by syphilis. Practising safe sex protects against – but does not completely prevent – the disease. </p>
<p>Testing is key. It involves checking the blood for antibodies against Treponema bacteria. The <a href="https://www.nature.com/articles/nrdp201773">test</a> is inexpensive and you get results within a day.</p>
<p>Anyone who is sexually active can ask for a <a href="https://www.cdc.gov/std/syphilis/Syphilis-June-2017.pdf">test</a>, but certain situations should trigger a test: pregnancy; HIV infection or sexually transmissible infections; and a partner with syphilis. <a href="https://bjo.bmj.com/content/early/2019/01/30/bjophthalmol-2018-313207">Doctors</a> may also suggest a test for rashes or ulcers, and for some inflammatory problems, such as uveitis. Everyone from the general public to our health-care professionals need to be more aware of syphilis.</p><img src="https://counter.theconversation.com/content/109658/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Justine R. Smith receives funding from the National Health & Medical Research Council (NHMRC) and the Ophthalmic Research Institute of Australia. She is a Science & Technology Australia Superstar of STEM.</span></em></p><p class="fine-print"><em><span>João M. Furtado does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>As ophthalmologists, we’ve noticed an uptick in cases of vision problems caused by syphilis. Practising safe sex is important for our eye health too.Justine R. Smith, Professor of Eye & Vision Health, Flinders UniversityJoão M. Furtado, Associate Professor of Ophthalmology, Universidade de São Paulo (USP)Licensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1006842018-09-06T11:16:27Z2018-09-06T11:16:27ZPenicillin was discovered 90 years ago – and despite resistance, the future looks good for antibiotics<figure><img src="https://images.theconversation.com/files/229603/original/file-20180727-106524-l87kc3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>When the <a href="https://theconversation.com/the-nhs-explained-in-eight-charts-91854">NHS turned 70</a> this year, I was reminded of another anniversary which has had an enormous impact on healthcare over many years. Penicillin is 90 this year. </p>
<p>Discovered in September 1928 by <a href="http://www.bbc.co.uk/history/historic_figures/fleming_alexander.shtml">Alexander Fleming</a>, it was first used as a cure when George Paine treated eye infections with it in 1930. A method for mass production was devised by Howard Florey and Ernst Chain in 1940, and it was first mass produced in 1942, with half of that total supply used for one patient being treated for streptococcal septicaemia. </p>
<p>In 1944, 2.3m doses were produced in time for the <a href="https://theconversation.com/the-military-power-economics-and-strategy-that-led-to-d-day-27663">Normandy landings</a> of World War II. And it was then that the miracle of penicillin became clear. Soldiers who had previously died from septicaemia were surviving.</p>
<p>Expectations rose. If penicillin could cure septicaemia, what about other serious infections like meningitis, pneumonia and kidney infections? Of course, we should use it for these, too. And what about nasty chest infections and troublesome sinusitis? Or inconvenient sore throats which could affect wedding days or job interviews – should these be treated with penicillin?</p>
<p>It seems (and for good reason) that we all wanted to be part of the 20th-century miracle that was penicillin. Patients didn’t want to be patients and doctors wanted to cure – why else did we come into medicine? </p>
<p>So antibiotic use grew and grew – and grew. Today, tens of millions of prescriptions are written in the UK every year, mostly by GPs and nurses in primary care. </p>
<p>But all is not well. Fleming was aware of the problem as soon as he discovered penicillin. Most bacteria were killed by the medicine, but others were immune, somehow able to resist the miracle. </p>
<p>And here is the paradox – in contrast to most medicines, the more we use antibiotics, the less effective they become. It’s because the bacteria multiply so rapidly – some every 20 minutes. If any one of the bacteria happens to survive antibiotic treatment, so do all of their offspring. And the antibiotic gives an immediate survival advantage to the resistant bacteria by indiscriminately destroying the competition. </p>
<p>The resistant bacteria affect us – our infections and hospital admissions last longer and are more expensive to treat. Over 25,000 people die every year from antibiotic-resistant infections in the UK and Europe. </p>
<p>But there is hope. There has been a massive, coordinated effort by the UK government, chief medical officers, NHS policy makers, NICE, the pharmaceutical industry, GPs, nurses, patients and academics. And <a href="https://theconversation.com/its-the-age-of-the-antibiotic-revolution-not-apocalypse-73476">we are making progress</a>. We have just witnessed <a href="https://www.england.nhs.uk/2016/03/antibiotic-prescribing/">the first reduction</a> (over 5%) in antibiotic prescribing in primary care for several years. </p>
<h2>Working with patience</h2>
<p>As a GP and professor of primary care who has observed the problem of antimicrobial resistance for over 20 years, I am optimistic about the future. More of my patients have heard about antibiotic resistance and seem to take it seriously. We all want to steward this precious resource for the next generation and I believe we will rise to the challenge. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/229601/original/file-20180727-106530-mtzziv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/229601/original/file-20180727-106530-mtzziv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=455&fit=crop&dpr=1 600w, https://images.theconversation.com/files/229601/original/file-20180727-106530-mtzziv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=455&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/229601/original/file-20180727-106530-mtzziv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=455&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/229601/original/file-20180727-106530-mtzziv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=572&fit=crop&dpr=1 754w, https://images.theconversation.com/files/229601/original/file-20180727-106530-mtzziv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=572&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/229601/original/file-20180727-106530-mtzziv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=572&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A plaque at St Mary’s Hospital in London.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/london-february-13-plaque-commemorating-discovery-185229575?src=z6hOzyS7QtRbZrdUIJLMVQ-1-91">Shutterstock</a></span>
</figcaption>
</figure>
<p>At the University of Bristol’s <a href="http://www.bristol.ac.uk/primaryhealthcare/researchthemes/disease-management/infection.html">Centre for Academic Primary Care Infection Group</a>, we continue to ask the big questions: why do some people experience lots of infections and others very few? How can we protect ourselves from acquiring infections in the first place? And are there effective alternatives to antibiotics? </p>
<p>Through <a href="http://www.bristol.ac.uk/primaryhealthcare/researchthemes/">our research</a> we already know that patients don’t necessarily want antibiotics – but they do want to know how best to manage infection symptoms. We’ve learned that even one course of antibiotics increases the chance that a patient in primary care will subsequently have resistant bacteria. We known that many infections last longer than we think, and knowing this can help us be more realistic about what to expect. And we discovered that ibuprofen is superior to paracetamol for relieving fever in children, and both alternated are superior to either alone. </p>
<p>Together with colleagues from across the world, our collective effort to answer the big questions will help patients, doctors, nurses and the NHS achieve the goal of effective antibiotic use. In this way, patients can continue to benefit from the miracle treatment that Fleming first discovered 90 years ago. So here’s to another 70 years of the NHS – and another 90 of effective antibiotics.</p><img src="https://counter.theconversation.com/content/100684/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Alastair Hay receives funding from the National Institute for Health Research (part of the NHS). He is a member of the NICE Managing Common Infections Antimicrobial Prescribing Guideline Group.</span></em></p>Alexander Fleming’s work has helped countless people over the last nine decades.Alastair Hay, Professor of Primary Care, University of BristolLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/957502018-05-02T10:41:49Z2018-05-02T10:41:49ZBacteria may be powerful weapon against antibiotic resistance<figure><img src="https://images.theconversation.com/files/216914/original/file-20180430-135844-3nv28t.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Bacteria in the dish on the left are sensitive to antibiotics in the paper discs. The ones on the right are resistant to four of the seven antibiotics.</span> <span class="attribution"><a class="source" href="https://en.wikipedia.org/wiki/Antimicrobial_resistance#/media/File:Antibiotic_sensitvity_and_resistance.JPG">Dr. Graham Beards</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>When I was a child, my parents gave me a sweet pink syrup to destroy the bacteria causing my sore throat. That memory is a testament to the power of antibiotics. But, through my research as a microbiologist over the past few years, I’ve learned that not only are some microbes immune to antibiotics but they can actually <a href="https://www.ncbi.nlm.nih.gov/pubmed/14798402">“eat” these drugs</a>, using them as a nutritious food to grow and multiply. </p>
<p>During the past decade, scientists have established that many <a href="http://doi.org/10.1126/science.1220761">soil-dwelling bacteria are able to resist</a> and <a href="http://doi.org/10.1126/science.1155157">eat the antibiotics</a> we depend upon to fight nasty infections. While this might feel like a rebuke from the world of microbes – a reminder that they can evolve to resist even our most powerful drugs – this is not all bad news. </p>
<p>My colleagues <a href="https://scholar.google.com/citations?user=3iE1s_wAAAAJ&hl=en&oi=ao">and I</a> in the lab of <a href="http://www.dantaslab.org">Gautam Dantas</a> have not only discovered how bacteria are able to eat the drugs that are supposed to kill them, but how this can be useful to people as well. We found we might someday be able to harness these antibiotic-munching microbes to clean up land and water contaminated with these medicines – a major cause of antibiotic-resistant superbugs. </p>
<h2>Why antibiotics make a good snack</h2>
<p>It may seem counterintuitive that microbes can eat the drugs that humans use to wipe them out. But from a bacterium’s perspective, antibiotics might be nothing more than a source of elements vital to life: carbon, hydrogen, oxygen and nitrogen. Furthermore, most of the antibiotics your doctor prescribes are made by, or derived from, fungi and bacteria living in the soil. So it makes perfect sense that these benign earthy microorganisms snack on the carbon compounds made by their soil-dwelling neighbors. </p>
<p>For the past 10 years, scientists in the Dantas lab have been investigating how bacteria pull off this seemingly unlikely feat. Now we think we’ve <a href="http://doi.org/10.1038/s41589-018-0052-1">cracked this mystery</a>. We have identified a collection of genes encoding enzymes necessary for microbes to consume penicillin (which <a href="https://www.nobelprize.org/nobel_prizes/medicine/laureates/1945/fleming-bio.html">Alexander Fleming</a> discovered in its naturally occurring form in 1928). We discovered that eating the drug is a two-step process in which the bacterium first disarms the antibiotic by breaking a piece called the “β-lactam warhead.” Without this, the remaining piece of penicillin is harmless and can be used as food, allowing the microbes to thrive in high concentrations of the drug. Second, the bacterium tears off a ring-shaped portion of the molecule and uses a dedicated family of enzymes to break it down further before eating the pieces.</p>
<p>Now that we understand which enzymes the bacteria use to disable the antibiotic, we can develop defense strategies and fight back. This is vital because antibiotic-resistant bacteria cause severe sickness in more than <a href="https://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf">2 million Americans, leading to more than 20,000 deaths annually</a>. These infections are more difficult and more costly to treat because they require long stays in the hospital. Every year this leads to <a href="https://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf">losses to the U.S. economy</a> directly due to the costs of treatment (US$20 billion) and indirectly due to lost productivity ($35 billion). </p>
<h2>Using microbes to eat contamination</h2>
<p>Ultimately we hope that we may be able to use our findings to curb one of the chief causes of antibiotic resistance: contamination of land and water. These natural resources are <a href="http://doi.org/10.1038/nature17672">polluted by sewage</a> runoff from farms where the <a href="https://amr-review.org/sites/default/files/160525_Final%20paper_with%20cover.pdf">animals are fed antibiotics</a> to fatten them up, and illegally dumped pharmaceutical waste or spills – particularly from <a href="https://epha.org/wp-content/uploads/2016/10/Superbugsinthesupplychain_CMreport.pdf">bulk manufacturers in China and India</a>. We believe we could remove these medicines through bio-remediation, which uses living organisms to clean up man-made messes. </p>
<p>While the bacteria that we identified in our study grew slowly when fed a diet of penicillin, we might be able to engineer new varieties that remove antibiotics more efficiently by speed-eating the drug. As a proof of concept, we cut and pasted genes from our soil microorganisms, as well as a previously discovered gene that we thought would have a similar function, into benign laboratory strains of <em>E. coli</em> bacteria and turned them into antibiotic-eating microbes.</p>
<p>Although this might sound simple, figuring out the genetic instructions for penicillin eating and inserting them into <em>E. coli</em> took several steps. First we <a href="http://doi.org/10.1128/genomeA.00653-17">sequenced the entire genetic content</a> – the genomes – of all four of the <a href="http://doi.org/10.1126/science.1155157">penicillin-eating bacteria that Dr. Dantas discovered</a>. This yielded a genetic roadmap of all the potential routes the bacteria could use to eat this antibiotic. By studying which genes were turned on by the bacteria while they ate penicillin, we learned which ones were most important.</p>
<p>To confirm that we had figured out the steps the microbes use to eat antibiotics, we broke these genes in one strain of the soil bacteria. This yielded mutants that were incapable of consuming penicillin, helping us to pinpoint which genes were needed to engineer <em>E. coli</em> to eat penicillin. </p>
<p>But the really interesting discovery was that penicillin eating requires two separate groups of genes to work together, beginning with an antibiotic resistance gene to break the toxic β-lactam warhead. Without this critical enzyme, the bacteria are unable to disarm the antibiotic, and without the enzyme responsible for removing the ring from penicillin, there is nothing to eat. </p>
<p>This suggests that we may be able to manufacture new strains of benign bacteria to remove antibiotics from the environment. This doesn’t mean that people can use antibiotics with impunity, but it might provide a safe way to curb the spread of antibiotic resistance in the future.</p><img src="https://counter.theconversation.com/content/95750/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Terence Crofts receives funding from the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Child Health and Development.</span></em></p>Antibiotic-munching microbes may prove useful for mopping up contaminated water supplies and land.Terence Crofts, Post Doctoral Trainee of Molecular Microbiology, Washington University in St. LouisLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/818202017-08-01T00:15:39Z2017-08-01T00:15:39ZWhy you may not need all those days of antibiotics<figure><img src="https://images.theconversation.com/files/180391/original/file-20170731-22154-my05rv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Green colonies of allergenic fungus Penicillium from air spores on a petri dish. Penicillin was the first antibiotic. </span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/green-colonies-allergenic-fungus-penicillium-air-498888628?src=PRxwQCFU_V49aCBySKiQ4A-1-1">Satirus/Shutterstock.com</a></span></figcaption></figure><p>A recent article in the British Medical Journal set off a bit of a firestorm with its claim that “<a href="http://www.bmj.com/content/358/bmj.j3418">the antibiotic course has had its day.”</a> The authors challenged the very widespread belief that you should keep taking every last dose of antibiotic prescribed by your physician even after you feel better. This advice has long been claimed to be <a href="https://www.statnews.com/2017/02/09/antibiotics-resistance-superbugs/">key to preventing antibiotic resistance</a>. </p>
<p>The challenge to that claim has sparked a <a href="https://www.rt.com/viral/397759-antibiotics-advice-contradicts-30-years-research/">backlash</a>, with physicians and public health officials expressing concern about an overly complex message that could result in encouraging patients to go rogue and ignore their doctors’ prescriptions.</p>
<p>All of this is a bit amusing to experts like me, who have been actively challenging this silly dogma for a long time, but without the recent media attention. So let me try to bring some clarity to the debate, which really isn’t that complex, so you understand what to do when your doctor gives you a prescription for antibiotics.</p>
<h2>Why taking too much of an antibiotic is drug abuse</h2>
<p>I’ll start with the bottom line first. It is absolutely false that continuing to take antibiotics after you feel completely better will reduce the emergence of antibiotic resistance. Quite to the contrary, it will very likely promote the emergence of antibiotic resistance!</p>
<p>How did we get to this point, with such a huge gulf between reality and dogma? And how could so much of the medical community have been so wrong for so long?</p>
<p>Let’s make one thing explicitly clear. Historically, doctors and patients have both been pretty dreadful about using antibiotics appropriately. We’ve long prescribed antibiotics out of fear and habit, not science.</p>
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<img alt="" src="https://images.theconversation.com/files/180390/original/file-20170731-22169-orlsri.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/180390/original/file-20170731-22169-orlsri.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=502&fit=crop&dpr=1 600w, https://images.theconversation.com/files/180390/original/file-20170731-22169-orlsri.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=502&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/180390/original/file-20170731-22169-orlsri.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=502&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/180390/original/file-20170731-22169-orlsri.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=630&fit=crop&dpr=1 754w, https://images.theconversation.com/files/180390/original/file-20170731-22169-orlsri.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=630&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/180390/original/file-20170731-22169-orlsri.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=630&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Alexander Fleming, who discovered penicillin, warned that the drug and other antibiotics could be overused.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File%3APenicillin_Past%2C_Present_and_Future-_the_Development_and_Production_of_Penicillin%2C_England%2C_1944_D17802.jpg">Ministry of Information Photo Division Photographer</a></span>
</figcaption>
</figure>
<p>Indeed, as far back as 1945, <a href="https://www.nobelprize.org/nobel_prizes/medicine/laureates/1945/fleming-lecture.pdf">Alexander Fleming</a>, the man who discovered penicillin in 1928, warned the public that people were taking penicillin to treat diseases not caused by bacteria, and that this unnecessary use of penicillin was going to breed out antibiotic resistance. He warned that those who so abused penicillin would be “morally responsible” for the deaths that ensued from penicillin-resistant infections.</p>
<p>He was right.</p>
<p>The sad thing is, society never did listen. Recent data confirm that our <a href="https://www.consumerreports.org/drugs/how-long-does-it-take-for-antibiotics-to-work/">use of antibiotics</a> has gotten no better in the modern era. </p>
<p>It has been estimated that 30 to 50 percent of <a href="https://www.cdc.gov/media/releases/2016/p0503-unnecessary-prescriptions.html">antibiotic use in the U.S. is unnecessary</a>. In my opinion, those numbers are rather hilariously low. I would that estimate 75 percent or more of antibiotic use is unnecessary. You see, I, and experts like me, have a more stringent definition of when antibiotic use is appropriate or not, which includes giving too long a course of antibiotics to patients who need them. </p>
<p>The truth is, we do not know how long a course of antibiotics is necessary to treat most types of infections. Even in the modern scientific era, the primary basis for the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5233409/">duration of most courses of antibiotics</a> is a decree <a href="http://www.thecreatorscalendar.com/constantine-and-the-week/">Constantine the Great</a> issued in A.D. 321 that the week would consist of seven days. That’s why your doctor gives you seven or 14 days’ worth of antibiotics!</p>
<p>If good old Constantine had decreed four days in a week, doctors would be prescribing antibiotics in four- or eight-day courses, rather than seven- or 14-day courses. I refer to seven- or 14-day antibiotic courses as “1 or 2 Constantine units” to underscore the absurdity of the basis for these durations.</p>
<p>But in the last two decades, we actually have had dozens of clinical trials published demonstrating that shorter courses of antibiotics are just as effective as longer courses (see table). </p>
<p><iframe id="Bp1nz" class="tc-infographic-datawrapper" src="https://datawrapper.dwcdn.net/Bp1nz/3/" height="400px" width="100%" style="border: none" frameborder="0"></iframe></p>
<p>Furthermore, the shorter-course regimens led to <a href="http://www.who.int/features/qa/stopping-antibiotic-treatment/en/">lower rates of antibiotic resistance</a>.</p>
<p>Enter <a href="https://vivo.brown.edu/display/lbrice">Dr. Louis Rice</a>, chair of medicine at Brown University. Rice has long been an international leader in antibiotic use and resistance. Ten years ago, he gave a lecture at a national infection meeting in which he challenged physicians to move to <a href="https://academic.oup.com/cid/article/46/4/491/296126/The-Maxwell-Finland-Lecture-For-the-Duration">evidenced-based, short-course antibiotic regimens</a>.</p>
<p>He then went a step further and became the first expert to publicly challenge the nonsense that continuing to take antibiotics after you feel better would somehow prevent the emergence of resistance.</p>
<p>Rice is the man who first called out that the emperor had no clothes. He traced the origin of this incorrect myth back through time. He discovered that the <a href="https://academic.oup.com/cid/article/46/4/491/296126/The-Maxwell-Finland-Lecture-For-the-Duration">myth appears to originate due to a general misunderstanding</a> of the findings in an article published in 1945, one of the first descriptions of penicillin therapy for pneumonia (lung infection). </p>
<p>This misunderstanding blossomed into the extremely pervasive, indeed erroneous, silly urban legend that continuing antibiotics beyond resolution of symptoms somehow helps reduce antibiotic resistance.</p>
<p>Not only is there absolutely no evidence that taking antibiotics past when you feel better will reduce antibiotic resistance, it doesn’t even make sense. The fact is, the longer you take an antibiotic for, the <a href="https://academic.oup.com/cid/article/46/4/491/296126/The-Maxwell-Finland-Lecture-For-the-Duration">greater the chance that antibiotic-resistant bacteria</a> will emerge in your body and in the environment around you.</p>
<p>There are some chronic infections, such as <a href="https://medlineplus.gov/tuberculosis.html">tuberculosis</a>, where you do indeed have to take long courses of antibiotics, not to prevent resistance, but rather to cure the infection. But for most acute bacterial infections, short courses of antibiotics result in equivalent cure rates, and with less chance of causing the emergence of antibiotic resistance among the bacteria in and on your body.</p>
<p>The World Health Organization (WHO) agrees that there is scant, if any, evidence for long courses of antibiotics, saying that “<a href="http://www.who.int/features/qa/stopping-antibiotic-treatment/en/">shorter treatments make more sense</a> – they are more likely to be completed properly, have fewer side effects and also are likely to be cheaper.” </p>
<h2>How to be antibiotic-smart</h2>
<p>So, what should we do about antibiotic courses? </p>
<p>Medicine in the 21st century is a team sport. You and your physician need to be partners in decision-making. If you are sick and your doctor mentions antibiotics to you, the first thing you should say is, “Hey, doc, do I really need the antibiotic?” </p>
<p>Doctors may otherwise prescribe an antibiotic even when you don’t need one, out of fear that you will be unhappy without the prescription. Flip the script on them. Help them to know that you’d prefer not to take the antibiotic unless it is really necessary.</p>
<p>If your doctor says, “Yes, I believe you have a bacterial infection and you need the antibiotic,” the next question is, “Okay, can we treat for a short course?”</p>
<p>Third, after you begin taking the antibiotics, if you feel much better before you complete the course, give your doctor a call and ask if you can safely stop therapy.</p>
<p>So, the bottom line is, doctors should prescribe as short a course of antibiotics as possible to treat your bacterial infection. If you feel completely well before you finish that course, you should be encouraged to call your physician to discuss if it is safe to stop early.</p>
<p>See, it’s not so complicated after all.</p><img src="https://counter.theconversation.com/content/81820/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Brad Spellberg receives funding from the NIH. In the last 12 months he has consulted for Entasis, Nabriva, Pfizer, Cempra, Bayer, Forge, Shionogi, Alexion, Synthetic Biologics, Paratek, and Ovagene, and he owns equity in BioAIM, Synthetic Biologics, Mycomed</span></em></p>We’ve been told for a long time that we must take all of our antibiotics. But maybe we didn’t need so many to begin with. Here’s why.Brad Spellberg, Chief Medical Officer, Los Angeles County+USC Medical Center, University of Southern CaliforniaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/713462017-01-18T15:01:37Z2017-01-18T15:01:37ZWhen it comes to big finds, scientists need more than just luck and chance<figure><img src="https://images.theconversation.com/files/152838/original/image-20170116-8769-cublv1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The author's backpack was hiding this almost complete therapsid fossil. Was finding it all down to luck?</span> <span class="attribution"><span class="source">Julien Benoit</span></span></figcaption></figure><p>The history of science abounds with stories about discoveries made by chance. One of the most famous cases, involves French physicist <a href="http://www.nobelprize.org/nobel_prizes/physics/laureates/1903/becquerel-bio.html">Antoine Henri Becquerel</a>, who accidentally discovered radioactivity by leaving a piece of granite on photographic paper in a drawer of his desk. Another, is the story of Scottish biologist <a href="http://www.nobelprize.org/nobel_prizes/medicine/laureates/1945/fleming-bio.html">Alexander Fleming</a>, who forgot his bacterial cultures at home when he went on holiday. They rotted – and Fleming discovered penicillin.</p>
<p>These charming stories showcase science’s most human aspect: men and women who make lucky mistakes that can save lives or change the world. Even scientists are happy to believe these tales, though they don’t do much justice to our colleagues’ expertise. </p>
<p>But is this really the way science works? Can anybody, scientist or not, rely on luck to make important discoveries? My own “lucky strike” as a palaeontologist – finding a nearly complete fossil of a pre-mammalian ancestor – helped me to understand that good science isn’t rooted in chance. It’s based on people with expertise being in the right place at the right time, equipped with enough knowledge to know what they’re looking at. </p>
<h2>A fossil find</h2>
<p>My moment of “luck” occurred in South Africa’s Karoo in 2015. I’d been invited to join an international team of palaeontologists led by Professor Bruce Rubidge and Dr Michael Day from the University of the Witwatersrand in Johannesburg. We came from Europe, South America and Africa to look for the fossils of <a href="http://www.newworldencyclopedia.org/entry/Therapsid">pre-mammalian therapsids</a>, which date back around 260 million years.</p>
<p>The Karoo is a semi-arid desert mostly populated by sheep and thorny bushes that covers a huge swathe of South Africa between Johannesburg and Cape Town. Hundreds of millions of years ago it was covered with lakes, rivers, dense primeval vegetation. Large reptile-like beasts roamed this landscape.</p>
<p>On the day in question we were fossil hunting between the towns of Sutherland and Fraserburg. There were rich pickings: Bruce and Michael had identified an area filled with fossil remains. So, we were in the right place. And, crucially, my shoes were totally wrong for the Karoo. Between the thorns and the heat, the plastic of my shoes had melted and their toes had been ripped open by thorns.</p>
<figure class="align-left zoomable">
<a href="https://images.theconversation.com/files/152839/original/image-20170116-8806-x8ur11.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/152839/original/image-20170116-8806-x8ur11.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/152839/original/image-20170116-8806-x8ur11.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=398&fit=crop&dpr=1 600w, https://images.theconversation.com/files/152839/original/image-20170116-8806-x8ur11.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=398&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/152839/original/image-20170116-8806-x8ur11.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=398&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/152839/original/image-20170116-8806-x8ur11.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/152839/original/image-20170116-8806-x8ur11.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/152839/original/image-20170116-8806-x8ur11.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Alexander Fleming.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
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</figure>
<p>So I sat down on an outcrop of sandstone that formed a natural bench, putting my backpack down next to me. A brief burst of rain brought a bunch of critters out from their hiding places to drink; an astonishing spectacle. When the sun returned, I felt ready to carry on. I picked up my backpack – and saw the beautiful, nearly complete fossilised therapsid skeleton it had been covering.</p>
<p>It was 30cm long and in great condition, and it has been right next to me, under my backpack all the time ! I couldn’t contain my enthusiasm, exclaiming, “How lucky am I?”. And that’s when I started thinking about “luck” in the context of scientific discovery. Was I that lucky after all?</p>
<h2>Serendipity and science</h2>
<p>Bruce and Michael, two experts in their field, had chosen our prospecting spot carefully based on what they knew. They had sent out a complete team of palaeontologists who knew what to look for. This doesn’t look like luck to me: it was probability in action. </p>
<p>This is the very essence of what we call serendipity: the art of creating the good intellectual, scientific and experimental context for a “fortuitous” discovery to happen. Fleming may well have discovered penicillin by chance, but the conditions were right because he had all the equipment and specimens he needed.</p>
<p>Becquerel would never have realised what he’d found if he hadn’t been carefully studying natural fluorescence. His existing knowledge allowed him to recognise a major discovery.</p>
<p>Maybe I discovered this skeleton by chance – or perhaps I found it because that was what we were looking for, in the right place and with the right people.</p>
<p>My humble fossil was certainly far from the level of Fleming and Becquerel’s discoveries. But it offered a valuable reminder that pure luck can’t account for scientific breakthroughs. Hours of work, and countless people and money are invested to create the right opportunity for discoveries to happen. Serendipity happens when scientists create their own luck.</p><img src="https://counter.theconversation.com/content/71346/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Julien Benoit receives funding from PAST and its scatterlings projects; the NRF; and the DST-NRF Centre of Excellence in Palaeosciences (CoE in Palaeosciences).</span></em></p>Good science isn’t rooted in chance. It’s based on people with expertise being in the right place at the right time, equipped with enough knowledge to know what they’re looking at.Julien Benoit, Postdoc in Vertebrate Palaeontology, University of the WitwatersrandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/637702016-09-07T05:00:29Z2016-09-07T05:00:29ZWeekly Dose: penicillin, the mould that saves millions of lives<figure><img src="https://images.theconversation.com/files/134720/original/image-20160819-12303-pka6ga.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A serendipitous discovery that saves millions of lives and garnered two Nobel prizes. </span> <span class="attribution"><span class="source">from www.shutterstock.com.au</span></span></figcaption></figure><p>In developed countries, infectious diseases accounted for most deaths until very recently. And in developing countries, infectious diseases remain the cause of death for a large percentage of the population. </p>
<p>It is in this setting that the discovery of penicillin in 1928 by Alexander Fleming was so instrumental in shaping modern health care. For the first time we had a reliable weapon against common infections; this was the start of the antibiotic era.</p>
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<a href="https://images.theconversation.com/files/136835/original/image-20160907-25260-2jsf3a.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/136835/original/image-20160907-25260-2jsf3a.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/136835/original/image-20160907-25260-2jsf3a.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=618&fit=crop&dpr=1 600w, https://images.theconversation.com/files/136835/original/image-20160907-25260-2jsf3a.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=618&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/136835/original/image-20160907-25260-2jsf3a.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=618&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/136835/original/image-20160907-25260-2jsf3a.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=777&fit=crop&dpr=1 754w, https://images.theconversation.com/files/136835/original/image-20160907-25260-2jsf3a.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=777&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/136835/original/image-20160907-25260-2jsf3a.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=777&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<h2>Discovery</h2>
<p>The serendipitous discovery of penicillin is testament to the importance of observation. Fleming noticed the mould Penicillium had antibacterial properties and deduced it must be secreting a substance that could kill bacteria – he named this substance penicillin. This led him to <a href="http://www.ncbi.nlm.nih.gov/pubmed/17187625">famously say</a>: “One sometimes finds what one is not looking for.”</p>
<p>As in many instances, there were clues in history that soil had healing properties for skin and wound infections. <a href="https://explorable.com/history-of-antibiotics">Healers in ancient Greece, India and Russia</a> used mouldy poultices (a moist package of herbs wrapped in cloth) to treat wounds. It was only in the early 1940s that laboratories such as Pfizer and USDA Northern Regional Research Laboratory developed methods to scale up to commercial production of penicillin.</p>
<p>The importance of penicillin is underscored by the fact its development yielded Nobel Prizes for physiology or medicine and chemistry in <a href="https://www.nobelprize.org/nobel_prizes/medicine/laureates/1945/">1945</a> and <a href="https://www.nobelprize.org/nobel_prizes/chemistry/laureates/1964/">1964</a> respectively for the scientists involved in its discovery and development. One of them was Australian Howard Florey, who then prime minister Robert Menzies <a href="http://adb.anu.edu.au/biography/florey-howard-walter-10206">described</a> as the most important man ever born in Australia in terms of world well-being. </p>
<p>The impact of penicillin after its discovery was immediately relevant. Its use in the treatment of <a href="http://www.historylearningsite.co.uk/world-war-two/medicine-and-world-war-two/">wounded soldiers in the second world war</a> decreased the risk of gangrene of the wound. This allowed time for surgical intervention, thus saving many lives and avoiding limb amputations during the war.</p>
<h2>How it works</h2>
<p>There are several ways to cause the destruction of bacteria, through disruption of the external wall or membrane that encases them, or interfering with the internal workings that allow bacteria to survive and replicate. </p>
<p>Penicillin antibiotics bind to penicillin-binding proteins on the surface of bacterial cells and block the bacterium’s ability to remodel its wall. Thus the wall is weakened and the bacterial cell starts to leak and die.</p>
<h2>Chemical structure</h2>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/134724/original/image-20160819-12274-g2p9t3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/134724/original/image-20160819-12274-g2p9t3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/134724/original/image-20160819-12274-g2p9t3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=942&fit=crop&dpr=1 600w, https://images.theconversation.com/files/134724/original/image-20160819-12274-g2p9t3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=942&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/134724/original/image-20160819-12274-g2p9t3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=942&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/134724/original/image-20160819-12274-g2p9t3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1184&fit=crop&dpr=1 754w, https://images.theconversation.com/files/134724/original/image-20160819-12274-g2p9t3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1184&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/134724/original/image-20160819-12274-g2p9t3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1184&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Chemical structure of penicillin.</span>
<span class="attribution"><span class="source">from www.shutterstock.com</span></span>
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</figure>
<p>Penicillin has more recently become a class of drugs, which all have a common chemical structure. </p>
<p>Penicillin antibiotics belong to a group called β-lactam antibiotics, due to the β-lactam ring that is essential for their effect on bacteria as it binds the antibiotic to the penicillin receptor.</p>
<p>Through modification of this basic penicillin structure, chemists have been able to expand the class to include many of the drugs we use to treat common infections today. </p>
<p>If you are on an antibiotic at the moment, there is a good chance it is from the penicillin class. Think Amoxil®, Dicloxacillin® and Augmentin®. </p>
<p>Tazocin®, another brand of penicillin, has recently become a commonly used medication to treat severe infections in hospitals due to its ability to kill many different bacteria.</p>
<h2>Resistance</h2>
<p>Over the past 50 years, since penicillin-based antibiotics have been widely prescribed to treat all sorts of infections, bacteria have started to become resistant with varying success. </p>
<p>Bacteria have, over time, changed the target receptor for penicillin, decreasing its effectiveness. They have also started to produce β-lactamases, proteins that disrupt the β-lactam structure of penicillin and inhibit its function.</p>
<p>By 1942, strains of <em>Staphylococcus aureus</em> were <a href="http://cid.oxfordjournals.org/content/45/Supplement_3/S165.full">already resistant to penicillin</a>. Today, around the world, many of the bacteria originally sensitive to the effects of penicillin are resistant. </p>
<p>On the other hand, many common bacteria still retain sensitivity to penicillin. Penicillin remains the antibiotic of choice for pneumonia in the community, as common bacteria such as pneumococcus are still overwhelmingly sensitive to penicillin.</p>
<h2>Use and cost</h2>
<p>Penicillin and related antibiotics are still the most common group of antibiotics to treat a broad range of infections from chest or throat infections to skin and soft tissue infections. In 2014, Australian patients filed <a href="http://www.pbs.gov.au/info/statistics/asm/asm-2014#_Toc425339268">5.8 million prescriptions</a> of Amoxil alone. </p>
<p>The decision to use these antibiotics depends on the site of the infection and the likelihood the patient may be infected by a resistant bacterium. </p>
<p>The cost varies widely between the different penicillins from about A$15 for a course of penicillin VK (an oral penicillin) up to A$70 for a course of Tazocin®. However, most are on the PBS, so the price to consumers is A$38.30, or A$6.20 for concession card holders.</p>
<h2>How they make you feel</h2>
<p>Penicillin and related antibiotics have been associated with life-threatening allergy known as anaphylaxis. Fortunately this is very rare and occurs in <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3255391/">less than 0.03% of patients</a>. Since penicillin antibiotics are commonly used, it is important people differentiate between serious allergy and mild side effects. </p>
<p>Penicillin is a very useful antibiotic group, so if the side effect is mild it is important to consider a re-challenge under the supervision of your doctor. There may even be cases where it is <a href="http://www.nejm.org/doi/pdf/10.1056/NEJM198505093121905">essential to desensitise patients</a> with severe reactions to penicillin.</p>
<p>The penicillins have a broad range of side effects. The most common are upset stomach, with nausea and/or diarrhoea and skin rashes. Rare side effects include liver and kidney inflammation. </p>
<p>And, like all antibiotics, penicillins can lead to infection with <em>Clostridium difficile</em>, an organism that causes severe diarrhoea, due to alteration of the normal gut bacteria.</p>
<p>Penicillins are generally safe to use with other medications. Occasionally, though, they can modify levels of certain medications such as methotrexate, which is used to treat cancer and autoimmune disorders.</p><img src="https://counter.theconversation.com/content/63770/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sergio Diez Alvarez is affiliated with the CEC Antimicrobial Stewardship Committee</span></em></p>The serendipitous discovery of penicillin is a testament to the importance of observation.Sergio Diez Alvarez, Director Of Medicine, The Maitland and Kurri Kurri Hospital, University of NewcastleLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/632652016-08-11T04:48:21Z2016-08-11T04:48:21ZA solution to antibiotic resistance may have been under our noses all along<figure><img src="https://images.theconversation.com/files/133501/original/image-20160809-18014-k1lfsf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Scientists are excited they've found potential new antibiotics – in us. </span> <span class="attribution"><span class="source">from www.shutterstock.com.au</span></span></figcaption></figure><p>Alexander Fleming <a href="http://www.bbc.co.uk/history/historic_figures/fleming_alexander.shtml">discovered penicillin</a> in 1928 and revolutionised the treatment of bacterial infections. Ever since then we have been searching for new antibiotics to address the myriad of infections humans encounter and the growing risk of resistance to them.</p>
<p><a href="http://www.nature.com/nature/journal/v535/n7613/full/nature18634.html">Researchers have now found</a> a bacterium in the human nose that produces an antibacterial product called lugdunin, which is able to suppress the common human pathogen <em>Staphyloccocus aureus</em> (commonly known as “Golden Staph”). This discovery marks a new frontier in the discovery of potentially useful antibiotics as the researchers found it in our own bodies.</p>
<h2>Where antibiotics come from</h2>
<p>Traditionally, antibiotics were sought in nature. This was based on the premise that all things on earth — plants, soil, people, animals — are teeming with microbes that compete fiercely to survive. Trying to keep one another in check, the microbes secrete biological weapons: antibiotics.</p>
<p>Serendipitously, and based on this principle, Alexander Fleming recognised the mould <em>Penicillium chrysogenum</em> produced penicillin when he noticed it inhibited the growth of common bacteria.</p>
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<a href="https://images.theconversation.com/files/133601/original/image-20160810-11853-x1dtph.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/133601/original/image-20160810-11853-x1dtph.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/133601/original/image-20160810-11853-x1dtph.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=408&fit=crop&dpr=1 600w, https://images.theconversation.com/files/133601/original/image-20160810-11853-x1dtph.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=408&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/133601/original/image-20160810-11853-x1dtph.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=408&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/133601/original/image-20160810-11853-x1dtph.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=512&fit=crop&dpr=1 754w, https://images.theconversation.com/files/133601/original/image-20160810-11853-x1dtph.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=512&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/133601/original/image-20160810-11853-x1dtph.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=512&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The mould that gave us penicillin.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/cambridgeuniversity-engineering/7186666813/in/photolist-7z134g-6ePSbM-bX4xHa-bX4xMr-ngndt7-bX4xEv">Engineering at Cambridge/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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<p>In the second world war, many wound infections were treated with a newly discovered antibiotic called tyrothricin, which was isolated from another organism, <a href="http://aem.asm.org/content/73/20/6620.full"><em>Bacillus brevis</em></a>. This was the first time researchers had turned to soil organisms to seek sources of new antibiotics. </p>
<p>A group of bacteria called actinomycetes was the source of almost half of the early antibacterial compounds found in nature. It is responsible for many of the commonly used antibiotics such as streptomycin (still occasionally used to treat tuberculosis), tetracyclines (still a first-line antibiotic used in treating pneumonia in Australia), chloromycetin (used as ear drops to treat ear infections) and the macrolide family, which includes common antibiotics such as azithromycin and clarithromycin (used to treat many common ailments such as stomach ulcers and chest and sinus infections).</p>
<p>In nature, antibiotics have been sourced from other bacteria, fungi, algae, lichens, plants and even some animals which use antibiotics to prevent bacteria from colonising the surrounding environment or creating disease.</p>
<p>Vancomycin, an antibiotic we use today to treat life-threatening infections, was discovered by a <a href="http://cid.oxfordjournals.org/content/42/Supplement_1/S5.full.pdf">chemist at a pharmaceutical company</a> from a bacterium in a soil sample sent from Borneo by missionaries. This single discovery has saved millions of lives around the world.</p>
<p>Over the last decade, few new antibiotic classes have been discovered. This means bacteria that are <a href="https://www.washingtonpost.com/news/to-your-health/wp/2016/05/26/the-superbug-that-doctors-have-been-dreading-just-reached-the-u-s/">becoming resistant</a> to the antibiotics we have may be untreatable in future.</p>
<p>In <a href="http://www.nature.com/news/promising-antibiotic-discovered-in-microbial-dark-matter-1.16675">early 2015</a>, researchers used modern techniques to culture a soil-derived bacteria, <em>Eleftheria terrae</em>. This produced a new antibiotic, teixobactin, which kills bacteria in a <a href="http://www.nytimes.com/2015/01/08/health/from-a-pile-of-dirt-hope-for-a-powerful-new-antibiotic.html?_r=0">unique and previously undescribed</a> way. </p>
<p>Researchers have been expanding the environments where they search for new antibiotics by focusing on areas around the world that are so hostile they might induce unique organisms to grow that produce previously undiscovered antibiotic substances. </p>
<p>A <a href="http://www.bbc.com/news/health-21457149">British group</a> has been searching the depths of the sea. <a href="http://scholarcommons.usf.edu/cgi/viewcontent.cgi?article=1124&context=ijs">Canadian researchers</a> are carrying out experiments on bacteria from deep within caves. Many other groups are isolating potential antibiotic-producing bacteria from <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3747354/">volcanoes, glaciers and deserts</a>. </p>
<h2>Why is this new discovery important?</h2>
<p>Humans have a <a href="http://www.the-scientist.com/?articles.view/articleNo/13313/title/-Ome-Sweet--Omics---A-Genealogical-Treasury-of-Words/">microbiome</a> that covers the body’s entire surface area, inside and out, and numbers around <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3426293/">10-100 trillion symbiotic microbial cells</a>. The bacteria that live inside each of us live in harmony and are able to suppress the growth of potentially harmful bacteria. </p>
<p>This is done through competition for nutrients and modification of the micro-environment, but also through the production of substances that suppress the growth of certain bacteria that normally are not found in humans. </p>
<p>Imagine if we could harbour the antimicrobial potential of our own microbiome. This new discovery opens the road to further studies harnessing the potential of our own bodies.</p><img src="https://counter.theconversation.com/content/63265/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sergio Diez Alvarez does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Alexander Fleming discovered penicillin in 1928 and revolutionised the treatment of bacterial infections. Ever since then we have been searching for new antibiotics.Sergio Diez Alvarez, Director Of Medicine, The Maitland and Kurri Kurri Hospital, University of NewcastleLicensed as Creative Commons – attribution, no derivatives.