Science Week 2017: Resistance – film screening and panel discussion

Dr Clare Sansom, Senior Associate Lecturer in Biological Sciences, writes on the screening of Resistance: not all germs are created equal and panel discussion on antibiotic resistance, which took place as part of Science Week 2017

resistance_panel-disc-3Antibiotic resistance is one of the most crucial issues facing humanity in the early 21st century, with some commentators even suggesting that it poses as serious a threat to civilization as climate change. It was therefore timely that one of Birkbeck Department of Biological Sciences’ contributions to Science Week 2017, with its strapline ‘Microbes in the Real World’, should tackle the issue. This took the form of a screening of an award-winning feature film from 2014, Resistance (subtitle: Not all germs are created equal) followed by an extensive and lively panel discussion. The four panellists were scientists from the department whose research is geared to the development of antimicrobial drugs: Dr Sanjib Bhakta, a Reader in microbiology; Professor Nicholas Keep, Executive Dean of the School of Science and a structural biologist; and two promising students from Dr Bhakta’s lab: PhD student Arundhati Maitra and MRes student Alina Chrzastek.

Not surprisingly, given the timeliness of the issue and (it has to be admitted) the size of the venue – the tiny Birkbeck Cinema in Gordon Square – the session was over-subscribed. After a short introduction by Dr Bhakta, who used his own research field of tuberculosis to set out the ‘global threat’ of drug resistance, the packed audience were treated to 70 minutes of engaging and at times chilling documentary. The film, by US producers Ernie Park and Michael Graziano or, collectively, Uji Films, uses a combination of archive footage, animation, interviews and personal stories to explain how we have arrived at a point where antibiotics are failing and what we need to do to ‘save antibiotics in order to save ourselves’. Although the film was made in the US and focuses on US policies and case studies, the problem it describes is a global one and it would not have been difficult to find equivalent examples in the UK.

The producers weaved three case studies of patients who had suffered antibiotic-resistant infections engagingly through the footage. We were introduced to a teenage lad who had been exceptionally lucky to survive drug-resistant pneumonia with some disability; a fit, middle-aged man who picked up methicillin-resistant Staphylococcus aureus (MRSA) while surfing and is now seriously disabled; and, most harrowingly, a mother whose 18-month-old baby picked up a new strain of MRSA and died within 24 hours.

The film’s narrators explained that all antibiotics are ‘poisons that kill bacteria but not us’; if they don’t kill the bacteria they make them stronger. Using antibiotics in such a way as to promote this rapidly sets up a ‘Darwinian battleground’ in which weak bacteria are knocked out but strong ones survive. This can happen very quickly because bacteria grow and divide so fast. In the words of scientist and author Maryn McKenna, we had the only effective way of killing bacterial pathogens and squandered it. And we have done this in three main ways: by over-use in the environment, in agriculture and in medicine.

The first two of these are particularly prevalent in the US and some Asian countries and less of a problem in Europe, where regulation is stronger. In the US, antimicrobials are used in everyday household products, sprayed on everything from fruit trees to kitchen counters. And once farmers had realised that constant small doses of antibiotics made livestock grow faster and fatter, even in crowded, unsanitary conditions, they were determined to keep doing so even though it ‘makes as much sense as sprinkling antibiotics on your children’s cereal’. Most US-produced meat and poultry is now contaminated with resistant bacteria, and occasionally this is multi-drug resistant. A Danish hog farmer, Kaj Munck, explained the sensible approach taken in Denmark where antibiotic growth promoters in animal feed were banned in 1995 following an extensive public debate. The Danish pig industry is still profitable, producing 28 million a year: about the same as the state of Iowa.

The beginning of the antibiotic era in human medicine coincided with World War II, when it was seen as a ‘miracle drug’ for curing infected wounds. Over-use, however, started very soon: penicillin was given to overseas sex workers, not to protect them from infection but to prevent their US military clients from becoming infected. The danger of resistance was known as early as 1945, when Sir Alexander Fleming told the New York Times that “in such cases the thoughtless person playing with penicillin is morally responsible for the death of the man who finally succumbs to infection.” Doctors who prescribe antibiotics inappropriately are often not morally wrong, or even thoughtless, but over-anxious to avoid mistakes when the chance of an infection being bacterial is low but not vanishingly so. Readily available, rapid diagnostic tests would go a long way towards preventing this type pf misuse.

It would not matter as much if antibiotics became ineffective if there were other molecules ready to take their places. However, the current antibiotic pipeline is weak, with few drugs coming through. Pharma companies can spend at least a decade and a billion dollars on developing a single drug, so it makes more sense to work on drugs like statins that patients must take every day. We must begin to encourage and reward companies that bring forward antibiotic ‘drugs of last resort’ rather than best-sellers. In short, the film concluded, the problem of antibiotic misuse is a classic example of ‘the tragedy of the commons’; one individual’s over-use of antibiotics may be neutral or even beneficial, but if everyone does it there will be a huge problem. To win the arms race against bacteria we may need to redesign all the processes through which we discover, use and protect antibiotics, and to ‘use our wits to keep up with their genes’.

Bhakta introduced the panel discussion with a short explanation of the molecular mechanisms through which bacteria acquire resistance to antibiotics. Bacteria evolve quickly, and almost all have acquired some resistance either intrinsically, through mutations, or by acquiring resistance genes directly from other species. This is an inevitable process but we have some control over how quickly it occurs: good antibiotic stewardship is as important as innovative science for winning the ‘arms race’ described in the film.

Bhakta’s group at Birkbeck is interested in tackling the problem of resistance through discovering new compounds with novel modes of action and by aiming to ‘re-purpose’ some over-the-counter medicines that are already in use for other indications. Drugs in this category will have already been shown to be safe and are therefore quicker and cheaper to develop. Keep summarised the role of structural biology in antibiotic discovery as one of determining the structure of bacterial proteins that might be vulnerable to attack by drugs and identifying compounds that can bind to and inhibit them. We are now often able to see directly how these structures are changed by mutations that increase (or decrease) resistance.

Bhakta chaired the discussion that followed, which was extensive and wide-ranging, taking in politics and economics as well as science and medicine. Several questions touched on the role and responsibilities of the pharmaceutical industry, which is reluctant to invest in drugs that will only be used for short periods. More drug discovery than ever before is taking place in academic labs and small companies, often working together; Maitra, whose Birkbeck Anniversary PhD studentship is part-funded by Wellcome, highlighted the role of the Trust in promoting links with industry. Re-purposing drugs that have already been used clinically is much cheaper than developing a molecule from scratch. MRes students in Bhakta’s lab, including Chrzastek, are testing common anti-inflammatory drugs against Mycobacterium tuberculosis and have found some potentially useful activity although the mechanism of action is still to be explored.

Other questions focused on the need for strict antibiotic control measures. In many European countries, including the UK, antibiotics are only available on prescription and cannot be used as growth promoters in animal feed. This ‘best practice’ needs to be replicated worldwide, but it will be an uphill struggle. Bhakta told the audience that he often visits countries in south and east Asia where resistance is prevalent and has seen antibiotics available over the counter there. In countries without strong, publicly-funded healthcare systems there are often incentives for doctors to over-prescribe drugs including antibiotics. And even where this is not an issue, patients need to be educated to think of antibiotics as drugs of last resort rather than demanding them for every upper respiratory tract infection.

It was perhaps inevitable that someone would ask the ‘Brexit question’: in this case, is there a danger that we would reverse some of our ‘best practices’ when we are no longer bound by EU regulations? Encouragingly, Bhakta doubted that anyone would want to get rid of rules with such clear benefits. He felt that the now inevitable move of the European Medicines Agency, which regulates all medicines marketed in the European Economic Area, from London – and the confusion about how the UK drug market will be regulated – does present a danger, to our strong research base. And however the politics develops the international collaborations that UK-based doctors, scientists and entrepreneurs have built up over decades must be maintained.

Other Science Week 2017 events:

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Science Week 2017: the source of human irrationality

Professor Nicholas Keep, Executive Dean of the School of Science, writes about Professor Mike Oaksford‘s Science Week 2017 talk on Tuesday 4 April
department-sliderProfessor Oaksford, the head of Psychological Sciences at Birkbeck, gave a talk on the source of Human Irrationality. There are proposed to be two systems for decision making.  System 1 is the older system shared with other animals and is fast and unconscious.  System 2 is slower and uses language and working memory to form a reasoned argument. It had been argued that irrational decisions arise from System 1 and System 2 is rational. However, Professor Oaksford argued the opposite. Studies of other animals such as starlings show that they are rational using System 1 and Professor Oaksford shows studies supporting the fast, unconscious response being rational in human. It is therefore, Mike argued, System 2 that leads to irrationality. It requires conversion of the unconscious processing into language and there is limited working memory to support system 2. Further, we do not (or cannot?) fully check all steps in our unconscious inference. The use of language can override our rational response and introduce errors of rationality.

What then is the advantage of language? It is that it allows us to be social and communicate our thoughts and plans with others thus accessing a wider range of experience and to store them in written form to recover them later. These social interactions should allow correction of our imperfect System 2 leading to better outcomes than System 1. I wold not be quite sure that this social correction is yet perfect judging by recent election results. There seems to be an ability to construct contradictory and mutually exclusive ‘rational’ views through social interaction.

Watch Professor Oaksford’s lecture on the source of human irrationality:

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Science Week 2017: fungi in heritage buildings

Dr Clare Sanson, Senior Associate Lecturer in Biological Sciences, writes on Sophie Downes’ talk on fungi and conservation in heritage buildings.mushroom-2198010_1920The Department of Biological Sciences’ contributions to Birkbeck Science Week 2017 focused on ‘Microbes in the Real World’. Apart from that over-arching theme, however, the two sessions could hardly have been more different. The Week kicked off with a lecture by PhD candidate Sophie Downes on the interactions between fungi and heritage buildings. As far as I am aware, Sophie is the first Birkbeck student to have given a Science Week lecture; she spoke with confidence and clarity, and held her audience well.

Nicholas Keep, Executive Dean of the School of Science at Birkbeck, introduced Sophie as a graduate of the University of Lincoln who had worked in textile conservation before moving to Birkbeck to study for a doctorate in Jane Nicklin’s mycology lab. She began her lecture by explaining the context of her research: her job had been based in a large Elizabethan house that had problems with pests and condensation, particularly in the show rooms. The need to find out how best to preserve and repair organic material in buildings like this one led directly to her PhD studies.

In the UK we have a huge number of historic buildings, many of which are popular tourist attractions and play an important role in the local economy, particularly in rural areas. A large number of these are maintained by the National Trust or English Heritage, and many are open to the public for the majority of the year. The thousands of visitors drifting through properties will affect the number and types of micro-organisms, particularly fungi, found there. Sophie’s project included a year-long survey, starting in the autumn of 2013, of fungi found in 20 historic buildings in England, Wales and Northern Ireland. These included cottages and wartime tunnels as well as the more usual castles and mansions, so the survey could be expected to provide a snapshot of fungi and fungal damage in a wide range of historic properties in the UK.

When we think of fungi, we tend to think of so-called ‘macro’ fungi: this category includes the mushrooms we eat and poisonous toadstools, but also dry rot. Micro-fungi are harder to spot, but they are at least as pervasive and colonise an enormous range of organic matter, producing spores. For example, they are responsible for the blue colouration often found on stale bread and preserves. Micro-fungi will colonise almost any organic object that they find in their way, which, in the context of a historic building, might include wood, tapestry, leather book bindings and silk wall hangings. Sophie used air sampling and sterile swabs to obtain representative fungal samples from one outdoor and four indoor locations at each building and recorded the position of and features in each room or area selected, with its temperature and relative humidity.

Sophie landed up with a total of 4,000 samples to analyse, which, given her limited time, was too many for wholescale sequencing. She started by separating these according to colour and morphology and then selected representative samples for DNA extraction and ‘barcode screening’, and fewer for DNA sequencing.  A total of 158 different fungal species from 77 genera were identified, with the most abundant genera being Aspergillus, Cladosporium and Penicillium. Some of the organisms found in smaller quantities, including fungal plant pathogens probably from the outside air and bacteria, were shed from visitors’ skin scales. Both the number of colony forming units and the diversity of fungal species recorded increased during the summer months.

Resident fungi can carry a small risk to human visitors to the buildings and perhaps a slightly higher risk to curators, given their higher exposure times. Fortunately, only a small fraction of the fungi identified were ‘nasty’ human pathogens, and all but one of these were classified in the lowest-risk group, Category 2. A larger number were recognised as of potential risk to particularly vulnerable individuals with damaged immune systems, and more still are only hazardous to the external environment.

The temperature, the height of the building, the type of room and amount of furnishings were found to be the most important factors in determining the extent of fungal growth within buildings and if high colony forming units would be observed, and the three most common fungal species in both the air and the swab samples – Penicillium brevicompactum, Cladosporium cladosporioides and Aspergillus versicolor – have frequently been reported in organic material in historical collections worldwide.

Fungi damage textiles and other organic materials by secreting enzymes that break down polymers, forming secondary metabolic products that cause further degradation. This process has important effects on the physical, chemical and mechanical properties of the materials. Sophie described how she had evaluated each of these, starting with the effect of fungal growth on the physical properties of cotton. Cladosporium infestation is known to cotton fibres, causing an unattractive colour change that cannot be removed by cleaning. She incubated new cotton strips with several fungal species and monitored them for 12 weeks using a technique known as colorimetry. Each fungus caused a gradual colour change, with Cladosporium causing by far the darkest stains. She also reconstructed images of fungi colonising woven cotton fibres in 3D with confocal fluorescence scanning microscopy.

Most fungi have long, filamentous structures called hyphae that secrete enzymes at their tips as they grow. These enzymes break down large and small organic molecules into nutrients; it is the breakdown of large molecules – polymers such as collagen, cellulose, fibroin and keratin – that cause chemical damage to heritage materials. Chitin and keratin are among the most complex organic substrates that fungi can digest and require several enzymes to break them down. Nevertheless, the three commonest species of fungi all managed to reduce the protein content of protein-containing fibres significantly, with Penicillium causing particularly serious damage to collagen. Fungal digestion also changed the local structure of protein fibres. And one net result of this chemical degradation is a change in the mechanical properties of the materials; for example, fungal infestation tends to cause silk to become more brittle.

But what are the implications of these results for the conservation of objects in historic buildings? All the test were conducted on modern materials, and aged ones, which are already worn, are bound to be more vulnerable. Sophie ended a fascinating talk by suggesting that this research will help to inform conservation protocols for the handling, treatment and risk factors involved with fungal contamination of historic collections.

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Science Week 2017: understanding climate change

This blog was written by Giulia Magnarini, Birkbeck graduate in Planetary Sciences with Astronomy and PhD candidate in Earth Sciences at UCL.scienceweekclimatechange850x450To understand current climate changes, we need to understand past events. However, using our existing climate model is really difficult.’ This is how Professor Andrew Carter began his talk on Earth’s long-term climate. Professor Carter’s research focuses on studying Antarctica in terms of climate changes.

Despite some persistent denial, evidence for an increasingly warm climate is clear. To provide a visual idea of the impact that the total melt of ice in Antarctica could have, Professor Carter asked the audience to imagine Big Ben under water up to the clock. Thames barriers would be ineffective and it is increasingly obvious how important research on climate change to tackle its consequential threats is.

Geological evidence for the first appearance of the ice sheet in Antarctica resides in sediments that date from 33 million years ago. The question is: why did Antarctica freeze over? Two hypotheses are proposed. The first one involved plate tectonics; as Antarctica separated from Australia and South America (circa 50 million years ago), ocean circulation changed and the strong Antarctic Circumpolar Current emerged, causing thermal isolation of the continent.

The second one takes reduction of atmospheric carbon dioxide into account. Historic data collected for ice volume, deep sea temperature and sea level all follow the same trend of the reconstructed amount of carbon dioxide in the atmosphere.

However, there are problems with both hypotheses. For instance, at the moment of the break, Antarctica was in a northern position and, although carbon dioxide was lower, overall temperature was warmer.

There are many difficulties in modelling over geological time. Nowadays, different models running for Antarctica show completely different results. Improving the quality of data is crucial because uncertainties are very high. On this point, Professor Carter has been conducting what is called ‘provenance analysis.’ This involves studying sand grains to locate their sources to better constrain past tectonic events and past environmental conditions. The grains that Professor Carter studies have typical shape due to ice erosion. Detrital zircons (very resistant minerals) are used to conduct U-Pb geochronological assessments to reconstruct the age distribution of the sediments. These ages are then compared with rocks from different areas for which age is known.

Oceanic drilling programs have been conducted within the ‘Iceberg Alley’. This is an area where icebergs are transported by currents and during the journey they deposit sediments. Results from sediment cores have shown that the grains come from other areas, meaning that they had been transported by icebergs, therefore implying that ice was already present on the continent at that time.

This new set of information can help improving tectonic models related to the opening of oceanic passages. Sampling the ‘Shag Rocks’, which are the only exposed part of the continental block within the Iceberg Alley, would be of benefit for this. Unfortunately, due to strong currents, this can be very difficult and dangerous.

Professor Carter concluded by pointing out the importance of better understanding the geology of this area because it was here that the Antarctic Circumpolar Current originated. This in turn had a significant implication on the global cooling of the planet. In fact, its influence reaches up to the northern hemisphere.

Therefore, more geological data can greatly improve the quality of climatic models. Better and more reliable climatic models will be fundamental to help future governments make important decisions.

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