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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Selecting the landing site for 2018 ExoMars Rover

This post was contributed by Birkbeck student, Anja Lanin. Anja attended Dr Peter Grindrod’s lecture, ‘Selecting the landing site for 2018 ExoMars Rover’ during Birkbeck Science Week 2016.

Mars and a rover

Over the last two years, specialist teams in Europe have been working on helping ESA select the landing site for the first European rover on Mars. This is not just a project for PhD-holders, even individual research findings from undergraduate students contribute to the realisation of this mission. Birkbeck students and staff, including the presenter of this talk, Dr Peter Grindrod, have been closely involved. In his talk ‘Selecting the landing site for the ESA 2018 ExoMars rover’, Dr. Grindrod not only brought to light the difficulties in finding an appropriate site in unexplored regions of Mars but also emphasised the problem of balancing safety, and scientific output.

Birkbeck on Mars!

Birkbeck scientists have been directly involved in developing the PanCam stereo-camera system, which is part of the ExoMars instrument payload, led by UCL’s Mullard Space Science Laboratory. This camera will be crucial for understanding the context of rocks and samples investigated by ExoMars.

Risky goals

The ‘search for signs of past and present life on Mars’ is the main goal of this mission, according to Dr Grindrod. The one billion Euro investment will initially rest on the Russian Proton rocket, with an 89% success rate, on the scheduled May 2018 launch date. The precious 300kg solar-powered rover payload is to land on Mars about 7 months later, via parachute and retro-rockets.

Dr Peter Grindrod

Dr Peter Grindrod

Looking for life, but where?

We learn from Dr Grindrod that the rover needs to land on some of the oldest Martian rocks (>3.6 billion years). Why? Geochemical analysis using orbital-based technology indicates that rocks in some of these oldest regions are sedimentary and characterised by hydrated (clay) minerals.

We know that on Earth clay minerals form from the interaction of rocks with water that is neutral in pH and suits terrestrial life. Some of the geologically younger rocks on Mars contain sulfate minerals formed under water-poor conditions and around life-unsuitable acidic water. So we need a site, as Dr Grindrod says, that at one point had some life-friendly water flowing through it depositing soft sedimentary rocks that the rover can get to and drill into.

Access forbidden – the contamination problem

According to Dr Grindrod, the rover is prohibited from landing in what are called ‘Mars Special Regions,’ areas where any terrestrial organisms unintentionally carried by the rover may survive. Thus areas potentially containing terrestrial life-supporting liquid water at present are a no-go. So scientists have been looking for a rover touch-down location in areas where there may have been life in the past but probably not at present.

Zooming in on a landing target

Mars isn’t small, but temperature constraints rule out areas near the cold poles and the seasonally warm southern hemisphere. Equally very hilly areas are also rover unsuitable due to the steep slopes. Keeping these constraints in mind, the most promising geological outcrops scientists were left with covered just 2% of Mars’ surface area. Finally, they had to consider that the rover could land anywhere within a still considerably large ca. 104 x 19 km elliptical area, rather than a particular spot.

Watch Dr Grindrod’s lecture

The chosen few

Two of the eight landing site proposals submitted throughout Europe came from the UK and both made it into the final four.

In the end a site called Oxia Planum was chosen as the destination for the 2018 launch. The location appears to be near the end of an ancient delta-like river drainage network and there may even be different layers present containing different types of clay minerals, possibly suggesting groundwater interaction. However, one problem with this landing site is that some of the surface is covered in small wind ripples – could the small 20 cm ExoMars rover wheels get stuck here??

For the back-up launch date in 2020 two back-up sites have been selected, Mawrth Vallis and Aram Dorsum. The latter location would place the rover near deposits of one of the oldest river systems (now inverted) on Mars and any landing spot would be conveniently located no more than 100 m from a relevant deposit.

Mars, the red planetWhat’s next?

If Oxia Planum for some reason is proved to be not to be safe enough more work is needed to decide which of the back-up sites is best for the alternative 2020 launch. In the end this decision will be up to ESA and the Russian Space Agency.

Let’s remember though, as pointed out by Dr Grindrod, once the rover touches down the scientific results are for us, for every scientist involved, for everyone whose money has contributed to the mission, not just the investors but also the public.

 

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Lost planetary worlds: Evidence of the unquiet early Solar System

This post was contributed by Birkbeck student, Anja Lanin. Anja attended Professor Hilary Downes’ lecture, ‘Lost Planetary Worlds’ during Birkbeck Science Week 2016.

Solar System

Professor Hilary Downes has been a research scientist in the Department of Earth and Planetary Sciences at Birkbeck for 30 years. Insights from her own and other workers’ research have left her with a strong interest in the evolution of the Solar System. As it turns out, the orderly Solar System we observe today in fact started out as everything but quiet and orderly. In its early days it was a place of violent collisions between planetary bodies. Many of these have been almost completely lost. Almost! We have evidence of their existence, ranging from the macroscopic to the elemental, and this was the subject of Professor Downes’ enthusiastic talk ‘Lost Worlds of the Solar System.’

Theory: Computer models

Starting her talk by showing a real image of a planet-forming region around stars, as observed by telescope, as well as computer models which together may suggest the organised formation of planets within an accretionary disk, Professor Downes moved on to theoretical considerations of a very different-looking chaotic early Solar System.

Computer simulations of Jupiter’s growth, for example, indicate that many planetary embryos were sent onto wildly eccentric orbits. Other models show planets such as Jupiter and Saturn moving repeatedly closer and then away from the sun causing gravitational chaos in the inner Solar System before the system became more settled.

Evidence from our Solar System planets – shaken and stirred!

The audience were then presented with some very odd and interesting facts about our planets. For one thing, they do not orbit the sun in the original plane (the location of the previous accretionary disk) of the Solar System. Some seem to defy the laws of physics by floating above and some below. Furthermore, some of the planets’ axial tilts have gone ‘wonky.’

While Jupiter and Mercury spin textbook-style perpendicular to the plane, all other planets have been knocked around to the extreme that Uranus has been completely knocked over and is now spinning parallel to the plane. Venus is even more special – it is rotating in the opposite direction to all other planets! These characteristics, according to Professor Downes, strongly suggest violent collisions of the planets with other planetary material.

‘Tangible’ evidence: meteorites within meteorites

So what happened to the impactors? We can actually study collisional space debris which comes to us in the form of meteorites. For many of these meteorites the parent body, for example a planet or an asteroid, is known, but, as Professor Downes emphasises, there are many parentless ungrouped meteorites. Perhaps the most interesting of these are brecciated meteorites which contain fragments of other meteorites. What do we learn from these fragments?

 

Real science reveals real mysteries….

As indicated in the talk, planetary science students at Birkbeck are actively accessing technology (e.g. electron microprobe) that allows them to study the mineralogy and basic chemical make-up of meteorites. This is one way that allows them to determine whether or not meteoritic material comes from a classified or unclassified parent body.

Something that cannot be analysed at Birkbeck yet!, but also yields very important clues, are oxygen isotope ratios. Each known planetary body has a unique oxygen fingerprint, so that previously unregistered ratios hint at lost parent bodies. Professor Downes, relating to her own group’s research, points out a particularly interesting brecciated meteorite fragment, which, surprisingly, turned out to be granitic, i.e. it is mineralogically and texturally similar to granites found on Earth (some of us recognise the rock from kitchen counter tops!).

However! – its oxygen chemistry indicates that it comes neither from Earth nor is it related to the other meteoritic material in which it was included as a fragment. It is therefore not related to the asteroid from which the rest of the meteorite is derived. In addition, a strange associated glass is high in sulfur (S) and chlorine (Cl), and no planet in the Solar System except Mars contains sulfur and chlorine. But the oxygen chemistry again suggests it is not from Mars. Thus, this glass may represent another lost planetary body or planet possibly disintegrated during the early collisional chaos!

There are many examples of odd, unexplained finds in meteorites. Even opal, which we recognise as a semi-precious stone, has been found by Profesor Downes and her colleagues, although its extraterrestrial origin is still unclear. Perhaps a water or ice-rich meteorite crashed into an asteroid and all that is left of this ice or water world is this little piece of opal?

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