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Vol. 40 No. 4 August 2018

Food Production

What is sustainable agriculture?

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Contents

The Biochemist Vol. 40 No.4

Food Production Editorial 3

Regulars

Features

Lifelong Learning Synthetic Biology Public Engagement

What is sustainable agriculture?

4

Leslie Firbank

Food production in an age of global warming and weirding

4

9

Stuart Thompson

AlcheMeat—how the future of animal production rests with biochemistry

13

Liz Specht

22

Colin Hill

Starch: the best and worst of nutrients Fred Warren and Suzanne Harris

18

VIRUS

VIRUS

VIRUS

MOULD

MOULD

MOULD

MOULD

Virus

Bacteria

MOULD

Bacteria

Virus

Careers A day in the life of a Policy Officer Tom Livermore

Meat by the molecule: making meat with 18 plants and cells RDA for microbes – are you getting your daily dose?

Science Communication Competition About cats, mice and behaviour-changing parasites

32

Victoria Bolton

Marie Gibbons

13

30

Corinne Hanlon

26

Policy Matters Driving developments in diversity Emma Sykes

36

38

News Events and Meeting Reports 42 Obituaries 44 Andre Darbre (1921 -2018) Hubert Greenslade Britton (1925 -2017)

Introducing the Industry Representative 46 Royal Society of Biology News 48 CEO Viewpoint 49 Book reviews 50 Cartoon 50 Prize Crossword 52

Virus

Bacteria

MOULD

Virus Virus Virus

BACTERIA

BACTERIA

BACTERIA

22 Mould

Mould

Mould

Coming up in 2018 30

The Brain Science and Space August 2018 © Biochemical Society 1

ADVERT SPACE Apply now for a Biochemical Society Diversity in Science Grant 2018 The Biochemical Society is offering four grants of up to £500 to individuals, groups, charities or not-for profit organizations to support and address issues relating to diversity in science.

To find out more and apply visit bit.ly/DiversityinScienceGrant Deadline for applications: 31 October 2018 Image: Dundee Women in Science Festival 2015

Editorial For advertising and inserts contact: Marketing Department Biochemical Society Charles Darwin House 12 Roger Street London WC1N 2JU tel.: +44 (0) 20 7685 2411; fax: +44 (0) 20 7685 2469 email: [email protected] Production by Portland Press Limited Editorial team: Anastasia Stefanidou, Emma Pettengale and Clare Curtis Design by Peter Jones Printed by Cambrian Printers Ltd, Aberystwyth Published by Portland Press Limited six times a year (February, April, June, August, October and December). The Biochemist © 2018 Biochemical Society ISSN 0954-982X (Print); ISSN 1740-1194 (Online) Charles Darwin House 12 Roger Street London WC1N 2JU tel.: 020 7685 2410 email: [email protected] website: www.biochemist.org Registered charity no. 253894 Subscriptions email: [email protected] Science Editor: Chris Willmott (University of Leicester, UK) Editorial Board: David Pye, Shane Hegarty, Harriet Groom, Matthew Lloyd, Patrick Walter and Heather Doran. The Editors are pleased to consider items submitted by Society members for publication. Opinions expressed in signed articles are not necessarily those of the Society. US agent: Air Business Ltd, c/o Worldnet Shipping Inc., 156–15, 146th Avenue, 2nd Floor, Jamaica, NY 11431, USA Periodicals postage paid at Jamaica, NY11431,USA. Postmaster: address corrections to The Biochemist, Air Business Ltd, c/o Worldnet Shipping Inc., 156–15, 146th Avenue, 2nd Floor, Jamaica, NY 11431, USA For all features: © 2018 The Author(s) This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY-NC-ND).

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Biochemistry Forever by Chris Willmott, Science Editor In July, I had the pleasure of participating in Biochemistry Forever, the 43rd Federation of European Biochemical Societies (FEBS) Congress in Prague. This was the second time I’d been to the annual FEBS jamboree and on both occasions I have been struck by both the scale and the quality of the event. Almost 2000 delegates from 67 countries were involved and were offered over 340 presentations to attend and the choice of nearly 1350 posters to read. The diversity of content might not suit everyone, and I know we at the Biochemical Society tend to prefer events with a narrower focus, but I appreciated the opportunity to bring myself (more) up to speed on a broad range of topics. A particular strength of the FEBS set-up is the work of their Young Scientists’ Forum. For the past several years, the YSF have organized an additional 3-day event in the same location, and directly preceding, the main Congress. A generous package covers most of the expenses of these early-career researchers to attend both events, including their accommodation and travel. There are spaces for about 100 YSF delegates (including two kindly supported by the Biochemical Society). Unsurprisingly the Forum is very heavily oversubscribed. As part of the arrangement, all YSF delegates also get the opportunity of a one-to-one consultation in which their CV is forensically critiqued by our own Keith Elliott. Among several very good offerings at the Congress, the standout for me was a final morning session on “Scientific (mis)conduct: how to detect (and avoid) bad science”. Although there was some consideration of overt fraud, a lot of the discussion focused on sloppy science, the “reproducibility crisis” and the hurdles that have to be overcome in order to correct errors in published work. A particular spotlight was shone on structural biology, both crystallography and cryo-EM. Here the implication seemed to be that many researchers looking to exploit these techniques lack either the chemical or statistical know-how to avoid making erroneous conclusions from their data. Within the emerging field of cryo-EM, there is a suggestion that many people are overstating the resolution of their data. There is an associated danger of circularity; data are used to refine an initial (possibly biased) model which, unsurprisingly, returns the initial model. There are agreed ‘gold standard’ procedures which greatly reduce the chances of over-interpreting the data, but it is relatively easy for the novice to come unstuck at some point or other. Issues of this sort are also found with other techniques. I am reminded of the “non-independence errors” and setting of inappropriate baseline controls which have led to some dubious observations using functional MRI, most famously the measurement of brain activity in a dead salmon (albeit set up to demonstrate the perils of misusing the technology). If you are interested in more about the specifics of that session, I have blogged about it at tinyurl.com/FEBSmisconduct. And if the FEBS Congress sounds like a suitable conference for you and/or early-career researchers in your group to attend, the next event is being held in Krakow in July 2019.

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August 2018 © Biochemical Society 3

Food Production

What is sustainable agriculture? Leslie Firbank (University of Leeds, UK)

We all want to eat food that is produced sustainably. But it’s not at all clear what that means in practice. Fundamentally, agriculture can be regarded as sustainable if it can continue to meet human needs whilst avoiding irreversible harm to the planet. The human needs are not just food, but include employment, leisure, social cohesion and the many ecosystem services provided by agricultural land that benefit people, including regulating water quantity and quality, carbon storage, maintaining landscapes of cultural and spiritual value, and providing homes for wildlife. Agriculture causes harm to the planet from habitat loss, carbon emissions, and pollution of air and water. Meeting these challenges is tough now, but it will only become more difficult as the human population rises and climate change becomes more difficult to cope with.

The key human need from agriculture is the provision of food for people. Homo sapiens is an omnivore, with requirements for carbohydrate, protein, fat, minerals and vitamins. One index of a healthy diet is the diversity of food items that one consumes; a simplified diet is likely to be low in certain elements and too high in others. Globally, there is more than enough food produced to feed everyone, yet an estimated 815 million people were undernourished in 2016, as a result of conflicts, inequality and economic slowdown. Malnutrition is not just about having too little food per se, it can be food of the wrong type. Obesity is becoming a chronic problem across the world, with an estimated 41 million overweight children under 5 in 2016, and adult obesity increasing everywhere. 28% of adults were classified as obese in North America and Europe in 2014, compared with around 13% across the globe. One way of dealing with food shortages and dietary imbalances is to grow more food. Indeed, it has been suggested that global food production must increase by around 60%. Yet this is becoming more difficult, as most of the land that is suitable for food production is already in use. Future growth in crop production therefore depends on increasing yields. For crops, this is likely to be where current yields are well below the potential, especially in sub-Saharan Africa. For livestock, yield increases seem most likely to come from increased output per animal and larger herds. Such increases in productivity have to be achieved in the face of problems including climate change, soil erosion, water shortages and declines in insect pollinators. Agriculture is already having a huge impact on the global environment. One measure is the Human

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Appropriate Net Primary Production, the proportion of plant production that is being used to support people. The estimates are highly uncertain, but it seems that around a quarter of net primary production was used by people in 2005, a value that is increasing. An estimated 37% of all land is used for agriculture, concentrated, of course, in areas with adequate climate and soils. The biomass of people and livestock combined outweighs that of all mammals and birds combined: the biomass of domestic poultry is about three times that of wild birds, while the biomass of livestock is over ten times greater than that of wild mammals. In most regions of the world, agriculture takes over 70% of freshwater, and emits around 24% of greenhouse gases. Clearly, agriculture needs to change if we are to keep the earth within a safe and just operating space. But how?

Let’s go vegan In the last few decades, the global demand for meat has risen. Around one-third of croplands are now used to grow feed for livestock, areas that could be used to grow crops for people. The greenhouse gas emissions (GHG) from the livestock sector account for around 14.5% of all human-induced emissions, and there are health risks involved in a high-meat diet. It’s not surprising that there are suggestions that a vegan diet will help make farming more sustainable. Yet there are strong arguments for not going 100% vegan globally. First of all, unless the diet is carefully managed with supplements, children on vegan diets are prone to nutritional deficiencies. Secondly, around 1 billion poor people around the world depend on livestock economically and for food. A reduction in livestock

Food Production

Figure 1. Urban farming in action. In Nairobi, a community fish farm uses wastes from a nearby brewery to feed flies, which are food for fish in these ponds. An urban fruit and vegetable smallholding is seen in the background. Photo credit: L.G. Firbank.

numbers, whilst avoiding competing for food that could be used by people (i.e. restricting to grazing land and food wastes) may result in a healthier diet, improved efficiency of land use and reduced GHG emissions. A recent study suggests that if this approach were applied to the US, cattle production would fall to around 45% of current levels; another one suggested that organic farming could feed the world in 2050, but only if diets changed and food waste reduced. A related discussion is about factory farming of livestock. The concentration of livestock into large units concentrates environmental impact, and is associated with low animal welfare. However, because the environment for the animals can be controlled, environmental impact per unit food can be lower than in free-range systems, while incidence of animal health problems can often be better controlled. The concentration of livestock like this also keeps the costs down, making meat and dairy products easier to afford.

Let’s go organic Organic farming does not rely on the artificial fertilizers and pesticides that underwrite much of intensive agriculture. The intention is to manage the natural processes, especially by improving soil quality. It does so by using crop rotations that include periods of grass, ideally with livestock, to rebuild soil nutrient levels and

structure (note a global organic, vegan farming system would be difficult to achieve…where would all the plant nutrients come from?). These improvements in soil structure confer resilience against more extreme weather conditions. Grass in rotations also help control weeds and diseases. The more varied landscapes that result tend to be richer in wildlife. Organic farming therefore should help reduce the environmental footprint and increase the resilience of farming against climate change. The main downside of organic farming is that yields are lower, especially across the whole rotation. The key argument against organic farming is therefore that, if adopted on a large scale, food production would fall. This point can also affect how the environmental footprint is perceived; if GHG emissions are measured per unit land, they are smaller on organic systems, but the difference pretty much disappears if measured per unit of food produced. Other distinctions between organic and nonorganic systems are harder to determine, especially now that pollution from pesticides and fertilisers can be much reduced thanks to new technology that applies pesticides and fertilisers precisely where they are needed. Evidence that organic food is of higher quality than conventional food, or that animal welfare is better, is patchy, and depends on how the particular farm is managed. This kind of discussion suggests that practices in organic and conventional agriculture are mutually exclusive, which is far from the case. If anything, best August 2018 © 2018 The Authors 5

Food Production practice in organic farming is being adopted more widely anyway. In Europe, bans in agrochemicals are encouraging the renewed uptake of cultural pest and weed control. In China, concerns about nitrate pollution are encouraging the use of organic manures instead of inorganic compounds, and in many parts of the world agricultural development is being steered towards Climate Smart Agriculture, which involves adapting to climate change by building soil resilience and ecosystem service delivery, often using techniques that are compatible with organic farming.

Let’s go GM

Figure 2. Cattle, Embrapa Research Station, Brazil. Photo credit: L.G. Firbank.

One of the key engines of improved agricultural performance is the advancement of crop and livestock genetics. This development has relied on fixing beneficial mutations into the organism’s genetic code. In the 1920s, it was discovered that the rate of mutations can be increased by exposure to radiation of chemicals, but the resultant changes were impossible to predict. Improvements in molecular methods in the late 20th century allowed a much more precise approach to plant breeding, of transferring desirable genes across species


barriers into crop plants. The first such genetically modified crops were made available for commercial use in the 1990s. However, there was a great deal of public opposition, especially in Europe where few GM food products are sold directly to consumers. The new crops were seen as unnatural, posing risks to human health and environment, reduced the diversity of crops, and were associated with increasing hold of multinationals on the agrifood system. On the other hand, GM has the potential to accelerate plant breeding to allow much more timely responses to changing pest and disease challenges, and to changing soil and climate conditions. Regulatory systems were installed around the world to manage their introduction. Regulatory systems were installed around the world to manage their introduction. The debate about GM remains lively. The technology has now moved on; it is now possible to edit genomes much more precisely using techniques including CRISPR/ Cas9, avoiding the need to move genes between species. CRISPR involves using an enzyme, Cas9, to edit DNA precisely and very cheaply, to insert or remove particular sequences. Such techniques are much cheaper and much more flexible than GM, and need not leave any

Food Production

Figure 3. Intensive dairy unit. The cattle are milked and fed with individualized rations on a rotary unit, which also checks weight and can provide an opportunity for health checks. Note the fans in the background to maintain temperature. Photo credit: L.G. Firbank.

imprints that are detectable in the progeny. Regulators are considering their response to CRISPR; in the US, they are not currently regulated, as they do not contain foreign DNA, although this situation is being reviewed. In Europe, the situation will be decided later in 2018, although a formal opinion earlier this year suggests that they need not be regarded as subject to GMO regulations. Whether this relaxed regulatory approach accords with public views remains to be seen. In truth, both the benefits and risks associated with the commercial production of GM crops have turned out to be rather muted. GM crops have neither saved the world nor put it at risk, but they have been commercial successes. However, the stakes will be higher in the future, as the technology allows a much wider range of modifications to a much wider range of plants and animals. For example, new modifications of biochemical pathways have enhanced the efficiency of photosynthesis of tobacco in the field by 15%. This has been achieved by speeding up the adaptation to fluctuating light by accelerating the conversion between violaxanthin and zeathanxin, and increasing the amount of photosystem II subunit.

Let’s spare land for biodiversity One of the big debates about farming is summed up as land sparing versus land sharing. The focus of debate is whether land should be used either for food or

conservation, or for both. Organic farming is seen as land sharing, as the levels of production are lower, the demand for land is higher, but wildlife can live on the land. Under land sparing, the idea is some land is used very intensively for food production, making it possible to free up land elsewhere that can be devoted to habitat and biodiversity conservation. The two models address different species; the farmland birds that might benefit from land sharing would not thrive in the spared tropical forests, or vice versa. Also, the land sparing model assumes that there is a simple trade-off over land. It’s not clear that the real world obeys these models. The link between agricultural production and biodiversity is not an inversely linear one, it is far more complex. In some situations, low levels of agriculture enhance biodiversity (this is especially true in the traditional, extensively farmed landscapes in Europe), and in others, biodiversity can enhance agricultural production (especially if the range of food products is increased to include some of the indigenous species). Nor is it clear that land allocation for the creation of nature reserves is influenced by agricultural prices. A more nuanced look at this issue recognizes that different parcels of land have different potentials; some are good for food production, some for supporting ecosystem services like flood management, some are good for biodiversity conservation. The trick is to find mechanisms so that different parcels of land are used appropriately, but at a larger scale the different requirements for food, housing, leisure and ecosystem services are provided. August 2018 © 2018 The Authors 7

Food Production Further reading •

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Figure 4. Arable landscape, East Anglia. Photo credit: L.G. Firbank.

Let’s use other ways of producing food There is increasing interest is developing new ways of producing food. The combination of hydroponics and LED lights is allowing indoor plant production at scale in urban settings; current emphasis is on high-value, small items, such as salad leaves. Such systems have the potential to provide dietary diversity at very local scales, just as smallholder systems involving feeding fish or chickens on food wastes (via insects) may be able to deliver protein. These systems demand little land or natural resources, and are creating opportunities for innovators around the world. The increasing success of culturing meat in a lab may also provide a commercially viable alternative to livestock production.

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Clark, M. and Tilman, D. (2017) Comparative analysis of environmental impacts of agricultural production systems, agricultural input efficiency, and food choice. Environmental Research Letters 12, 064016 Eshel, G., Shepon, A., Shaket, T., Cotler, B.D., Gilutz, S., Giddings, D., Raymo, M.E. and Milo, R. (2017) A model for ‘sustainable’ US beef production. Nature Ecology and Evolution 2, 81–85 FAO World Agriculture Towards 2030/2015, the 2012 revision. Gao, C.X. (2018) The future of CRISPR technologies in agriculture. Nature Reviews Molecular Cell Biology 19, 275–276 Intergovernmental Science: Policy Platform on Biodiversity and Ecosystem Services (IPBES) (2017) The assessment report on pollinators, pollination and food production of the intergovernmental sciencepolicy platform on biodiversity and ecosystem services www.ipbes.net/system/tdf/downloads/ pdf/individual_chapters_pollination_20170305. pdf?file=1&type=node&id=15248 Kromdijk, J. Głowacka, K., Leonelli, L. Gabilly, S.T., Iwai, M. Niyogi, K.K. and Long, S.P. (2016) Improving photosynthesis and crop productivity by accelerating recovery from photoprotection. Science 354, 857–861 OECD FAO Agricultural Outlook www.agri-outlook. org/. UN Sustainable Development Goals www.un.org/ sustainabledevelopment/sustainable-developmentgoals/ Kumar, S., Chen, W., and Novak S. (2017) Trait stacking in modern agriculture: application of genome editing tools. Emerging Topics in Life Sciences 1 (2) 151-160

Looking ahead Something has to change over the next few decades if we are to meet our societal needs for food without going beyond the earth’s capacity. But there is no single offthe-shelf answer. First of all, food consumption needs to be smarter; eating a balanced diet with less waste. But this is not a simple a decision for the individual, as dietary choices are related to poverty and quality of life. Sustainable agriculture cannot fix this problem. We need more responsibility for the whole food chain at more local levels; currently it feels too remote for many people to really care about it. On the farm, there is no single pathway to sustainability, no single label that gives us the assurance we would like. But all pathways will involve the more intensive application of knowledge to land management, recognizing that land, soil and water are vital natural resources to be nurtured.

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Les Firbank is an agro-ecologist. He was brought up on a small farm in northern England, took a degree in zoology before researching into interactions between farming and the environment. His early work focussed on weeds and crops, before moving to the Centre for Ecology and Hydrology where he led large scale studies on the environmental effects of set-aside, organic farming and GM crops. He moved to North Wyke Research where he developed the concept of an intensive, farm-scale research platform to look at the mechanisms underpinning more sustainable farming. He is now Professor in Sustainable Agriculture at the University of Leeds, addressing the sustainable intensification of agriculture. Email: [email protected]

Food Production

Food production in an age of global warming and weirding Stuart Thompson (University of Westminster, UK)

Some estimates suggest that we will need to double food production by 2050, and do so despite the effects of climate change on crop yields. The competing demands of agriculture and human populations upon water supplies can only become more extreme with time and are likely to be exacerbated by the impact of increased evaporation due to global warming and changes to rainfall patterns. Therefore, this article will examine some of the ways that we can produce food using less water.

The world population passed 7 billion in 2011 and we anticipate that it may reach 9 billion by the year 2040. How will we feed so many? In addition to the simple increase in the number of mouths, many in the developing world, entirely reasonably, aspire to the lifestyles of populations in the developed world. Therefore, it has been estimated that by 2050 we may need to increase agricultural production to twice that of 2005, and we must achieve this without substantially adding to the area that we farm.

of the conflicting demands of agriculture and human populations. Supply of water to crops is still one of the main limitations upon agricultural productivity, but intensive irrigation can bring its own problems, such as the build-up of salts known as ‘salinization’, which may affect 70% of agricultural soils by 2050. For these reasons, the main focus of this article will be some of the ways that we might produce food using less water and under conditions when less water is available.

This cannot possibly be achieved if crop yields only improve at their current rate, and climate change is expected to make producing even what we do now more difficult. For example, models of the effects of increased temperature on wheat suggest that we can expect yields to fall by about 5% per 1°C of warming. Projections suggest that even if the signatories to the United Nations Framework Convention on Climate Change Paris Agreement stand by their commitments, the world will warm by between 2.6 and 3.1°C by 2100. Every bit as alarming is what has sometimes been called “global weirding”. This refers to the effects of carbon emissions on weather patterns. It has almost become a cliché to greet each unexpectedly hot (or cold) day as a sign of global warming, but it seems that there has already been a significant increase in the frequency of ‘abnormal’ climatic events such as droughts and floods. We can expect that this tendency will become more extreme as temperatures continue to rise.

It may be worth initially considering why water is so important for agriculture. In photosynthesis, plants collect carbon dioxide from the air and convert it into carbohydrates. A small amount of water is used for photosynthesis itself and slightly more for growth, but the vast majority is simply evaporated, typically 97% or more of the total taken up. This is because carbon dioxide used in photosynthesis must first be absorbed by moist surfaces inside the leaves of the plant. If carbon dioxide can reach these surfaces from the atmosphere, water can also escape in the opposite direction. Plants restrict this loss by closing pores in their leaf surfaces, known as stomata, but if they do, they also prevent carbon dioxide getting in. Therefore, in land plants, water loss and photosynthesis are inextricably linked. To gain carbon (and in crops, that is what provides dietary calories) you must lose water.

One of the primary ways that heat affects yields is by increasing water evaporation. Even now it seems that rainfall patterns may be altering as a result of climate change, and water supplies are under pressure as a result

In plants, carbon dioxide is usually directly captured by an enzyme known as ribulose bisphosphate carboxylase/ oxygenase or RuBisCO. The carboxylase conducts the reaction in which carbon dioxide is fixed, converting

Turbocharged rice

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Food Production one molecule of ribulose bisphosphate and one of carbon dioxide into two molecules of phosphoglycerate. This is referred to as ‘C3 photosynthesis’ because phosphoglycerate, the first product in this process, has three carbon atoms. However, RuBisCO doesn’t distinguish well between carbon dioxide and oxygen. As a result, it will sometimes instead catalyse a reaction between ribulose bisphosphate and a molecule of oxygen, producing one molecule of phosphoglycerate and one of the two-carbon molecule, phosphoglycolate. The carbon in phosphoglycolate has to be recycled via a complex and wasteful series of reactions distributed between the cell’s chloroplasts, peroxisomes and mitochondria. Phosphoglycolate is formed by the ‘oxygenase’ activity of RuBisCO and this and the metabolic processes used to recycle it are referred to as photorespiration. This is a relatively limited problem at low temperatures, but evaporation increases approximately exponentially as the temperature increases, forcing plants to close their stomata to prevent water loss. As a consequence, carbon dioxide levels inside the leaf fall. At higher temperatures, RuBisCO differentiates less well between carbon dioxide and oxygen, and the ratio of dissolved carbon dioxide to oxygen is reduced. These effects mean that the rate of the oxygenase reaction rises and photorespiration becomes a greater and greater burden upon the plant as temperatures rise, potentially wasting 30% of the carbon fixed by C3 photosynthesis. However, a number of species have evolved a solution to this. In these plants, carbon dioxide (or more specifically bicarbonate) is initially combined with phosphoenolpyruvate (PEP) by the enzyme PEP carboxylase to form oxaloacetate. Oxaloacetate has four carbon atoms and so this is referred to as ‘C4 photosynthesis’. Note that C4 plants still use RuBisCO, but it is concentrated in specialized cells surrounding the leaf veins called ‘bundle sheath cells’. The advantages of initially capturing carbon dioxide as oxaloacetate are that PEP carboxylase has a greater affinity for carbon dioxide than RuBisCO, and more importantly, that after conversion into malate or aspartate for transport, it can be concentrated in the bundle sheath cells. C4 plants thereby boost carbon dioxide levels around RuBisCO and virtually eliminate losses due to photorespiration. This makes them more productive at higher temperatures and they need less water because they can open their stomata less. Additionally, because they use their RuBisCO more efficiently they need less of it, and therefore less nitrogen for protein synthesis. C4 species seem to have begun to evolve when carbon dioxide levels in the atmosphere dropped about 25 million years ago and expanded to dominate tropical grasslands across much of the Earth from about 15 million years


ago when continental movements caused many areas to become more arid. Grasslands across the world today divide between those dominated by C3 and C4 species depending on their temperature and rainfall patterns. Perhaps unfortunately, the majority of our cereals originated from temperate C3 species. Some crop species carry out C4 photosynthesis, including maize, sugar cane and sorghum, but most do not, including wheat and rice. It has been estimated if rice could be modified to carry out C4 photosynthesis its yields could be increased by as much as 50%. We expect that this would reduce its water use, help it to withstand global warming, and perhaps also reduce fertilizer use (remember that C4 species need less nitrogen, and converting nitrogen for fertilizer itself contributes to global warming). About half of the world’s population depend on rice as a staple crop and so C4 rice could be a game changer. An international collaborative project funded in part by the Bill and Melinda Gates Foundation is underway to achieve this. Unfortunately, when genes for the main enzymes required for C4 photosynthesis were simply inserted into rice, very little C4 carbon fixation resulted. Nor did the plants thrive. All of the metabolites involved in C4 photosynthesis are already present in plant cells and so it was not terribly surprising that adding new enzymes attuned to a different metabolic environment was disruptive. However, C4 photosynthesis is one of the most striking instances of convergent evolution, having apparently arisen independently more than 60 times. Therefore, recapitulating this process in rice ought to be feasible and this has become one of the main thrusts of the C4 rice project. Interestingly, the evolutionary steps involved seem to start with a ‘streamlining’ of the photorespiratory reactions and so the problem may form part of the

Figure 1. A tomato plant that had not been watered for a number of weeks. Growth of one of the fruits was being monitored and it was still expanding at this point. Vascular development affects whether water flow reverses and fruit contraction occurs under water stress and is often observed, but this extreme instance illustrates the degree to which resources can sometimes be directed into fruit development under water deficit. Reproduced with permission from Davis, W.J. et al., J Exp Bot (2000) 51, 1617–1626.

Food Production

Figure 2. (a and b) Cell walls of sunflower hypocotyls imaged using cryo-SEM (scale bars = 25 µm for both micrographs). (a) A hypocotyl pre-treated with control buffer and (b) is a hypocotyl that had been exposed to a water potential of –0.62 MPa, equivalent to a moderately severe water stress, generated using polyethylene glycol (PEG, osmotic pressure π = 0.62 MPa). Note the thinning of the walls in (b), presumably due to withdrawal of water from them, which is especially notable at the cell corners. The mechanical effects on the walls of applying and removing water potential treatments were tested using hypocotyl walls being stretched by a constant load, and are illustrated in (c). A treatment equivalent to applying a water stress of –0.62 MPa (by replacing control buffer with buffer containing PEG) caused a transient increase in length but considerably reduced the extension rate thereafter and reversing this led to a prolonged increase in the extension rate of the material. Reproduced with permission from Evered, C. et al., J Exp Bot (2007) 58, 3361–3371.

solution. A recent report by Jane Langdale and colleagues describes replication of one of the early steps in this pathway, using maize transcription factors to bring about formation of enlarged chloroplasts and mitochondria in the cells surrounding the leaf veins in rice, as is seen in C4 species. This is a promising development, but the project is ambitious and will not reach its goal in the near future. Furthermore, even after C4 photosynthesis has been first achieved in one type of rice, it will have to be integrated into a range of other varieties for widespread use.

Tricking crops into using less water Another approach that may bring benefits more quickly takes advantage of plant responses to water stress. It has been known since at least the 1940s that plants in drying soil conserve water by closing their stomata. However, it was not clear whether this happens when shoots and leaves of the plants directly experience water stress, or can be caused by a signal from their roots to prepare them for a reduced water supply before its effects start to bite. An elegant experiment was devised to test this in fruit trees grown with their roots split between two pots. They were kept hydrated by watering one pot, but the roots in the other pot were exposed to a drier environment. The trees closed their stomata even though water potential measurements showed that the aerial parts of the plant were receiving plenty of water. This seemed to confirm that the roots in the dry pot were indeed sending some sort of message that caused the shoots to conserve water.

Particularly persuasive was that the test plants went back to behaving like the well-watered controls when the roots in the dry pot were cut off. These experiments provided a useful insight into plant responses to water deficit, but it has turned out that the same methods can also be exploited to produce crops using less water. Researchers in Australia examined whether it would be possible to grow grapes for winemaking more efficiently by watering the roots on only one side of each row of vines while leaving roots on the other side unwatered. Their results were spectacular. The total grape harvest was the same but the vines used 30% less water and the grapes were better for wine making. The reason for this observation shed light on why the trick worked. It was because side shoots stopped growing and so more light was falling on the grapes, which consequently improved the quality of wine produced. As we would expect, when the vines closed their stomata it reduced photosynthesis and therefore total biomass accumulation, but the resources that they did have were directed to the fruit. Presumably, this is an adaptation to ensure that the plant reproduces despite environmental stresses. The degree to which this can occur is illustrated by the tomato plant in Figure 1. It was overlooked and left in a system that had been recording growth of one of the fruits when the investigator went on holiday. It was noticed that the fruit being tested was still growing when they returned 2 weeks later, even though the rest of the plant was obviously experiencing catastrophic water stress. August 2018 © 2018 The Authors 11

Food Production In many cases the reproductive tissues of our crops are the part we eat, whether these are fruits or seeds, and so we can often improve water efficiency by taking advantage of the way that plants protect their next generation. ‘Partial rootzone drying’ and other systems of ‘regulated deficit irrigation’ have now been shown to reduce the quantity of water required for food production without substantially decreasing the yield in a wide range of species, including tomato, sunflower, oilseed rape, mango and rice.

Further reading

Taking control of growth

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Water shortages can also affect plant development and we may also wish to control this in our crops. It will frequently be beneficial to maintain root growth to reach water supplies deeper beneath the soil, and keeping leaves and shoots growing to increase total photosynthesis may be the best strategy if there is a limited but reliable water supply. However, if conditions are more severe it could be better to reduce the leaf area from which water can be lost. Plant growth needs water because (as with all organisms) cells are mostly made of water, but for plant cells to expand their cell walls must also be stretched by turgor pressure. Their rate of growth can fall either if the pressure drops, which can result from reduced water availability, or if the walls become stiffer.

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It seems that drought signals such as the plant hormone abscisic acid often reduce growth by causing cell walls to become less extensible in the tissues they affect. However, it has also become apparent that water plasticises plant cell walls, and that moderate stresses could in principle inhibit growth by pulling water out of them. Figures 2a and 2b illustrate that treatments equivalent to water stresses can reduce the water content of walls of sunflower hypocotyls and make them thinner, and Figure 2c shows that these treatments also affected the rate at which they could be stretched. It seems likely that the strength of this effect depends on how strongly the polysaccharides of the walls can hold onto water and therefore that wall composition could be used to control growth of plant tissues under water stress. This has not yet been explored but may offer a tool to influence crop physiology under drought conditions. This article barely touches upon the wide and diverse range of approaches that researchers are exploring to protect our food production in light of the challenges that we face. Our odds of finding solutions will be best if we keep as many options in mind as possible, not least because different things may work best in different areas and for different crops. However, the success of at least some of these projects will be critical for the history of the 21st century.

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Tilman, D., Balzer, C., Hill, J. & Befort, B.L. (2011) Global food demand and the sustainable intensification of agriculture. Proc Natl Acad Sci 108, 20260–20264 Liu, B., Asseng, S., Müller, C., Ewert, F., Elliott, J., Lobell, D.B. et al. (2016) Similar estimates of temperature impacts on global wheat yield by three independent methods. Nat Climate Change 6, 1130–1136 Rogelj, J., den Elzen, M., Höhne, N., Fransen, T., Fekete, H., Winkler, H. et al. (2016) Paris Agreement climate proposals need a boost to keep warming well below 2°C. Nature 534, 631–639 Fischer, E.M. & Knutti, R. (2015) Anthropogenic contribution to global occurrence of heavy-precipitation and high-temperature extremes. Nat Climate Change 5, 560–564 Marvel, K. & Bonfils, C. (2013) Identifying external influences on global precipitation. Proc Natl Acad Sci 110, 19301–19306 Bräutigam, A. & Gowik, U. (2016) Photorespiration connects C3 and C4 photosynthesis. J Exp Bot 67, 2953–2962. Sage, R.F., Sage, T.L. & Kocacinar, F. (2012) Photorespiration and the evolution of C4 photosynthesis. Annu Rev Plant Biol 63, 19–47 The C4 Rice Project: Driven by the future needs of developing world agriculture. https://c4rice.com Betti, M., Bauwe, H., Busch, F.A., Fernie, A.R., Keech, O., Levey, M., et al. (2016) Manipulating photorespiration to increase plant productivity: recent advances and perspectives for crop improvement. J Exp Bot 67, 2977–2988 Wang, P., Khoshravesh, R., Karki, S., Tapia, R., Balahadia, P., Bandyopadhyay, A., et al. (2017) Re-creation of a key step in the evolutionary switch from C3 to C4 leaf anatomy. Curr Biol 27, 3278–3287 Gowing, D.J., Davies, W.J. & Jones, H.G. (1990) A positive root-sourced signal as an indicator of soil drying in apple, Malus × domestica Borkh. J Exp Bot 41, 1535–1540 Stoll, M., Loveys, B. & Dry, P. (2000) Hormonal changes induced by partial rootzone drying of irrigated grapevine. J Exp Bot 51, 1627–1634 Davies, W.J., Bacon, M.A., Thompson, D.S., Sobeih, W. & Rodríguez, L.G. (2000) Regulation of leaf and fruit growth in plants growing in drying soil: exploitation of the plants’ chemical signalling system and hydraulic architecture to increase the efficiency of water use in agriculture. J Exp Bot 51, 1617–1626 Mousavi, S.F., Soltani-Gerdefaramarzi, S. & Mostafazadeh-Fard, B. (2010) Effects of partial rootzone drying on yield, yield components, and irrigation water use efficiency of canola (Brassica napus L.). Paddy Water Environ 8, 157–163 Zhanga, H., Xuea, Y., Wanga, Z., Yang, J. & Zhang, J. (2009) An alternate wetting and moderate soil drying regime improves root and shoot growth in rice. Crop Science 49, 2246–2260 Thompson, D.S. (2008) Space and time in the plant cell wall: relationships between cell type, cell wall rheology and cell function. Ann Bot 10, 203–211 Evered, C., Majevadia, B. & Thompson, D.S. (2007) Cell wall water content has a direct effect on extensibility in growing hypocotyls of sunflower (Helianthus annuus L.). J Exp Bot 58, 3361–3371

Dr Stuart Thompson is a Senior Lecturer in Plant Biochemistry at the University of Westminster. His research interests include the influence of water on plant development, the biomechanics of plant growth, and the intersection between these areas. He lectures in a wide range of areas including the history and philosophy of science and environmental ethics. Email: [email protected]

Food Production

AlcheMeat—how the future of animal production rests with biochemistry Marie Gibbons (Harvard Medical School, The Good Food Institute, USA)

Innovations in regenerative medicine, stem cell biology, tissue engineering, and biopharmaceutical production are responsible for saving countless lives and completely transforming healthcare. But what if this research could be applied to more than individual medical treatments? New applications within these fields could further address public safety concerns, global malnourishment, environmental issues, and animal abuse. In fact, these types of studies could lead to prevention of many of the diseases they initially set out to treat! Foci within these areas, such as telomerase expression, cell differentiation, induced pluripotency, three-dimensional tissue formation, recombinant protein production and CRISPR, are now being used for something entirely different – making meat.

The majority of the human population regularly eat meat. Meat is high in protein, convenient, affordable and, for most people, delicious. But once you scratch the surface of the process behind eating meat, you will come to find that it’s not all it’s cracked up to be. Given that several types of meat are classified as carcinogens and packed with cholesterol, sodium and saturated fats, it is easy to correlate consumption with the top two killers in America: cancer and heart disease. Many foodborne illnesses stem from contaminated meat products, 80% of our antibiotics are fed to farm animals, and zoonotic diseases are easily spread within the concentrated animal feeding operations that source the majority of our meat products. Animal production is responsible for more greenhouse gas emissions than all planes, trains and automobiles combined, leading the way in man-made climate change. Desertification, deforestation, erosion, acidification, eutrophication and species extinction are all extremely damaging results of intensive farming practices. The 9 billion pigs, cows, chickens, turkeys, and other land animals farmed and slaughtered for food each year in the US alone might appreciate a change within the food system. Despite the growing body of evidence relating meat production and consumption to these health, environmental and welfare concerns, we still can’t get enough of it. Seeing as the world probably won’t be going vegan anytime soon, we need a solution, and fast. Luckily, biotechnology is offering new approaches.

Clean meat research is a focus within the field of ‘cellular agriculture’, a movement made up of scientists, entrepreneurs and activists hoping to change the food system for the better by growing animal products without animals.

Clean meat in the making Clean meat has been in the making for over a century, starting with 1900s Nobel laureate Alexis Carrel, who grew chicken heart muscle in a dish for months on end. William Churchill predicted we would be growing chicken-free chicken breasts by the 1980s, and artist Oron Catts cooked up some clean frog meat for an exhibition in 2003. It wasn’t until 2013, however, that the field really got going, when Dutch physiologist Mark Post served up some Google-funded clean burgers during a broadcast in London. This led to a burst of research and startups in the field. In addition to beef, companies and academic institutions have now produced clean chicken, duck, turkey, fish and pork, with several products expected to hit the shelves within the next 3 years. So how does one grow clean meat, what are some of the challenges the field must overcome, and how can interested scientists apply their expertise to help raise the steaks? In theory, the process is quite simple. Get your hands on some animal cells, seed them into a bioreactor containing the proper nutrients and environmental August 2018 © 2018 The Authors 13

Food Production conditions for proliferation, and when you have enough cells, combine them with a meat-like scaffold and grill up some burgers. In practice, however, there is still a bit of work to be done before you’ll find any clean meat options at your local drive-thru. Until then, it is up to us scientists to perfect the process of clean meat production.

What type of cell to sell? Like our current meat production methods, clean meat begins with a cell. Clean meat scientists are experimenting with several different cell types, including tissue-specific cells, embryonic stem cells, mesenchymal stem cells and induced pluripotent stem cells. While there may be several optimal cell types for clean meat production, there are certainly some traits that would be extremely beneficial for each cell type of interest to possess. These include fast proliferation rates, unlimited growth potential and differentiation flexibility. Tissue-specific cells, such as the musclebased satellite cells and myoblasts, fat-producing adipocytes and plentiful fibroblasts, can be harvested from a simple biopsy the size of a sesame seed. They proliferate well in culture, easily differentiate into their tissue-specific cell type, and with a little guidance, can differentiate into other cell types as well. However, tissue-specific cell types may not be able to proliferate for more than a few months before undergoing senescence – at least, not without a bit of genetic editing, spontaneous immortalization or experimental media additives. We continue to study the exciting process of controllable immortality within tissue-specific cell types for clean meat applications, but scientists have also turned to stem cells. Embryonic, mesenchymal and induced pluripotent stem cells are able to continuously

Figure 1. Why buy the whole pig when you can grow the sausage?

evade cell ageing, possibly due to their ubiquitous expression of a very special protein: telomerase. Telomerase is a longevity-promoting protein that acts by adding telomeres to the end of our chromosomes, thus allowing cells to continuously divide indefinitely without the threat of chromosome shortening or fusion. While the exact role of telomerase in immortality varies across species, many farm animal cell lines are able to grow indefinitely when telomerase expression is

Figure 2. Myoblasts easily differentiate into multinucleated muscle fibres when crowded and exposed to low nutrients


Food Production upregulated. Another benefit of stem cells is their ability to theoretically differentiate into any cell type.

chemically defined, serum-free media formulations for specific cell types.

Maintaining stem cells in an undifferentiated state, however, can be troublesome. Many researchers are working on methods that establish better control over stem-cell fate. Additionally, stem cells can be costly and difficult to grow in culture when compared with tissuespecific cell types. Other issues may arise from stemcell harvests. Multiple harvests from animals for clean meat are not required, as a single cell could potentially lead to the production of 30,000 times the global annual meat demand if allowed to double exponentially over a 3-month period. However, initial isolations are needed to establish cell lines, and many may not like the idea of harvesting cells from animal embryos. Like tissuespecific cell types, however, mesenchymal stem cells are found throughout adult tissues, rendering the need for embryonic harvests unnecessary.

While we are moving further and further away from harvesting blood from fetal cows in the name of science, large-scale cell culture media formulations still face some challenges in the form of cost. Serumfree media is made of several different growth factors that must be produced recombinantly, in a similar fashion to that of biopharmaceutical production. This process can be pretty pricy, but as production scales up, the costs will drop dramatically. The push for scaled growth factor production means more affordable clean meat AND cell culture media for biomedical research.

Perhaps even more appealing is the option of induced pluripotency. Researchers are now able to take isolates from several different sources, such as blood samples, skin scrapings, cheek swabs, hair follicles, or feathers, and turn these tissue-specific cells into pluripotent stem cells. These cell harvests are much less invasive than embryonic collections or tissue biopsies, and produce cells that share the same characteristics as a stem cell. It is worth noting that the easiest way to induce pluripotency currently involves genetic modifications, and while more natural methods are possible, additional research is needed to boost efficiency.

Not all media is good media Once you have your hands on some animal cells, you need to provide them with the nutrients, chemical signals and environmental conditions required to promote fast and controllable growth. This is accomplished by using a suitable cell culture medium. In the past, researchers have supplied cell cultures with all the necessary factors normally found within the body by going straight to the source of cell nutrients – blood; fetal cow blood, to be exact. We can’t very well claim to produce animal-free animal products if we are relying on feeding our clean meat cells with fetal cow blood. Biomedical researchers have, however, begun ‘steering’ away from animal-based media additives for several reasons. Variations in batches, unknown pathogens, and undefined additives found in fetal bovine serum lead to unanticipated and hard-to-replicate results within cell culture experiments. These drawbacks have led several research supply companies to produce

Other options for serum-free media additives involve co-culturing with cells like liver, which naturally produce growth factors within the body. A plethora of growth factor analogues and functional domains could be hiding within the unexplored proteomes of several different plant species, and it may be possible to synthesize growth factors from plant proteins as well. We can also potentially remove growth factors from the media entirely by creating cells that can make their own growth factors. Furthermore, we could edit cells to bypass the initial growth signalling pathways and grow independently of growth factors, assuming they are given appropriate nutrients and maintained under the proper pH, temperature and osmotic pressure. While there is still much to learn about clean meat media, we are getting closer every day.

Bioreactors: where bio and farm meet Now that you have your cells and know what to feed them, it’s time to find them a home. However, the perfect bioreactor is still up for debate. Adhesion-based setups are intuitive options, as the majority of cell types found in meat are anchored to other cells when housed in the body. But adhesion-based reactors may involve more complicated and time-intensive harvests, extra detachment enzymes and unwanted premature differentiation and senescence when compared with alternative production methods. Given the difficulties associated with anchorage-dependent bioreactor systems, suspension-based culture may be more promising in the long run. In fact, stir-tank bioreactors are the go-to setup for many large biopharmaceutical companies. Using yeast, bacteria and even mammalian cells such as Chinese hamster ovary cells, we are currently growing cells to produce recombinant proteins on a very large scale. This process, however, yields only a small amount August 2018 © 2018 The Authors 15

Food Production of the intended product – the protein isolate. Clean meat production, on the other hand, is not focused on producing recombinant proteins; we want the entire cell. So while biopharma is constantly seeking to increase protein production yield, clean meat systems will be able to harvest much more product, and undergo much less downstream processing. The cost of suspension-based recombinant protein production may be high at the moment, but considering the anticipated higher yields and simple processing of clean meat cell proliferation, it is safe to assume that this system will be much more affordable. As we continue to scale production, clean meat proliferation methods could lead to decreased costs associated with biopharmaceutical production as well, creating more accessible medicine.

Figure 3. Future meat production facilities may look more like a brewery than a barn.

Scaffolds: the matter of the meat When it comes to clean meat scaffolding, we have several different options. Scaffolding can be used as a means of growth, in addition to serving as textural and structural support. We are still a few years away from a rack of ribs, a turkey leg or a T-bone steak, but the texture and appearance of processed meats such as burgers, meatballs, sausages, cold-cuts and nuggets can be easily reproduced thanks to the growing plant-based meat field.

As we expand on our clean meat options, borrowing research from the field of whole organ synthesis may prove successful when attempting to replicate the organoleptic properties of current meat products. Here, the clean meat field holds an advantage over growing entire organs. While organ developers must create tissues that are able to perfectly function without being rejected by the body, clean meat just has to taste good and not kill anyone.

Food for thought

The main hurdles left within plant-based meat involve the replication of taste and animal-based protein content, both of which can be addressed with cell-based meat production. Plant-based scaffolds include meaty fruits, veggies and fungi such as coconut, jackfruit, artichoke and mushroom. We can also create textured wheat, bean and pea isolates that can be produced to form a meat-like product with the help of extrusion methods. Synthetic scaffolds utilized within regenerative medicine are also promising. While these types of scaffolds may initially be harder to produce when compared with the ease of harvesting crops or operating an extruder, they offer more control in terms of texture, shape, nutrient distribution and even cell-type differentiation. As we learn more about the intercellular interactions involved in cell fate, it may be possible to design scaffolds that can promote different types of differentiation within different areas of the scaffold. With this insight, we could grow marbled, meat-on-the-bone products, all from a single cell source seeded on to an edible or degradable scaffold.


Figure 4. The world’s first clean turkey meat, created by seeding turkey muscle cells on to de-cellularized jackfruit fibres

Food Production We are constantly gaining a better understanding of the biochemistry involved in cellular metabolism and proliferation. As we make new discoveries about novel cell signalling pathways and molecular interactions, and as computational biology, machine learning and data-scraping technologies advance, so too will our knowledge of and applications for biochemistry. There are still many hurdles within clean meat science – we must determine the most efficient cell types, affordable media formulations, scalable bioreactor processes and satisfying scaffold designs. But as we continue to optimize the clean meat system, we add to the discoveries within regenerative medicine, stem cell biology, tissue engineering and biopharmaceutical production.

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Advances in the field could lead to meat without transfats, do-it-yourself meat-growing kits and meat options during space travel, all while addressing the many issues associated with current meat production. What’s more, clean meat research could help find cures for muscular diseases, uncover the mysteries of aging, explore tools for organ synthesis and supply our growing population with more accessible biopharmaceuticals. More and more industrial leaders and academic institutions are getting involved with the research, and the release of clean meat to the market is so close we can taste it. Just as we are no longer draining whales for oil or whipping horses for transport, soon we won’t need to kill a pig in order to bring home the bacon.

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Marie Gibbons, MS, is a Clean Meat Scientist at Harvard Medical School and Academic Research Advisor with The Good Food Institute. She holds an MS in Physiology, a BS in Zoology, a minor in Psychology, and has 10 years of veterinary experience. Marie is using her passion for animal welfare and interest in biological science to explore and promote the cellular behaviours needed for large-scale muscle cell production using serum-free media. Email: [email protected]

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Bouvard, V., Loomis, D., Guyton, K.Z., Grosse, Y., Ghissassi, F. El, Benbrahim-Tallaa, L. et al. (2015) Carcinogenicity of consumption of red and processed meat. The Lancet Oncology 16, 1599–1600 Burdick, J.A. & Vunjak-Novakovic, G. (2009) Engineered microenvironments for controlled stem cell differentiation. Tissue Engineering Part A 15, 205–219 Food & Agricultural Organization of the United Nations (2006) Livestock’s Long Shadow: environmental issues and options Florini, J.R. & Roberts, S.B. (1979) A serum-free medium for the growth of muscle cells in culture. In Vitro 15, 983–992 Genovese, N.J., Domeier, T.L., Telugu, B.P.V.L. & Roberts, R.M. (2017) Enhanced development of skeletal myotubes from porcine induced pluripotent stem cells. Sci Rep 7, 41833 He, S., Li, Y., Chen, Y., Zhu, Y., Zhang, X., Xia, X. & Sun, H. (2016) Immortalization of pig fibroblast cells by transposon-mediated ectopic expression of porcine telomerase reverse transcriptase. Cytotechnology 68, 1435–1445 Kim, Y.M., Park, Y.H., Lim, J.M., Jung, H. & Han, J.Y. (2017) Induction of pluripotent stem cell-like cells from chicken feather follicle cells. J Animal Sci 95, 3479–3486 Micha, R., Michas, G. & Mozaffarian, D. (2012) Unprocessed red and processed meats and risk of coronary artery disease and type 2 diabetes: an updated review of the evidence. Current Atherosclerosis Reports 14, 515–524 Modulevsky, D.J., Lefebvre, C., Haase, K., Al-Rekabi, Z. & Pelling, A.E. (2014) Apple derived cellulose scaffolds for 3D mammalian cell culture. PLoS One 9, e97835 Poore, J. & Nemecek, T. (2018) Reducing food’s environmental impacts through producers and consumers. Science 360, 987–992 Qin, L.-L., Li, X.-K., Xu, J., Mo, D.-L., Tong, X., Pan, Z.-C. et al. (2012) Mechano growth factor (MGF) promotes proliferation and inhibits differentiation of porcine satellite cells (PSCs) by down-regulation of key myogenic transcriptional factors. Mol Cell Biochem 370, 221–230 Shridhar, S., Klanert, G., Auer, N., Hernandez-Lopez, I., Kańduła, M.M., Hackl, M. et al. (2017) Transcriptomic changes in CHO cells after adaptation to suspension growth in protein-free medium analysed by a speciesspecific microarray. J Biotechnol 257, 13–21 Xu, S.-Q., Sell, C., DuBois, G.C. & Baserga, R. (1997) A novel growth stimulating activity from BRL-3A cell conditioned medium. Cell Proliferation 30, 295–307


Food Production

Meat by the molecule: making meat with plants and cells Liz Specht (The Good Food Institute, USA)

Our notion of meat has undergone a redefinition in recent years. New technologies for producing meat are challenging our assumptions regarding whether meat production need involve animal farming at all. In this article we’ll explore opportunities in the growing fields of plant-based meat and clean meat, both of which are predicated upon the concept of deconstructing and reconstructing meat at the cellular and molecular level.

Rethinking meat: a critical challenge for our era Global demand for meat is expected to increase by more than 70% between 2011 and 2050. This prediction is based on a combination of population growth and increased per capita demand especially in developing countries, where meat consumption has historically been relatively low. As this demand skyrockets, it is clear that the considerable resource burden, environmental harms, climate implications and public health risks

posed by intensive industrialized animal agriculture are growing reasons for concern. At its most dire, there is a looming food security issue that cannot be ignored. There is simply not enough arable land – even if all the world’s remaining forests were cleared – for us to continue producing meat in the way that we currently do. Incremental efficiency improvements are insufficient to get us past the fundamental thermodynamic Sisyphean challenge of funneling calories through a living, breathing, metabolizing animal. One could hardly dream up a more inefficient system for creating food.

Figure 1. Companies like Beyond Meat (plant-based chicken strips, left-hand side) and Impossible Foods (plant-based burger, right-hand side) have reimagined meat using plants. These newer products appeal to omnivores who are seeking to swap out meat at some meals — so-called “flexitarians” — which is driving the unprecedented growth of the plant-based meat category.


Food Production A pioneering collection of companies, academic researchers, and public and private funders are betting on the ability to make meat without the animal. There are two main approaches driving this paradigm shift. The first is developing plant-based meats: products that exhibit the taste, texture and full consumer experience of meat but are made from plant-sourced protein and other ingredients. (While “plant-based meat” is the common industry term, this approach also encompasses ingredients sourced from beyond the plant kingdom – such as fungi, algae, and even bacteria.) The other approach is to grow clean meat, which is genuine animal meat produced by cultivating animal cells rather than the whole animal. Meat is undergoing a rebranding campaign. In the burgeoning realm of meat alternatives, meat is no longer defined by its origin or composition. It is defined by its structure, taste and role on our plate.

Food is biochemistry, and meat is no exception Our deep cultural associations with food entice us to position it in the realm of the social sciences or perhaps even the arts. At its essence, however, food is humanity’s romanticized version of Luria broth in a petri dish: it is the nutrient and energy source for our metabolizing bodies. But to a biochemist, there is something striking about the simplicity of this notion too. At the core, food is comprised of a set of biochemical molecules that, when combined and finessed in just the right way, can

impart the complex sensory experience we associate with a particular food or meal. Thus, the task of fundamentally rethinking meat entails viewing its creation as a matter of biological happenstance. Meat isn’t an immutable, optimized food source. Rather, it is the confluence of events that resulted in animal muscle tissue of certain species appealing to our taste buds when prepared in certain ways. Understanding this allows for distilling meat’s essence down to distinct molecular signatures (chemical and structural) that can be recapitulated with new source materials. For example, can we use a combination of heat, a pH shift and shear stress to convert globular plant storage proteins into a fibrous, textured strand resembling the long chains of myosin and actin found in animal muscle? Can we canvass the plant kingdom for a protein that binds a haem group – and the iron bound within that haem group – to impart the metallic, meaty taste of red meat? Can we prospect for proteases and crosslinking enzymes that readily turn insoluble plant substrates into highly functional food ingredients? Indeed, plant-based meat companies like Beyond Meat and Impossible Foods have already answered questions like these with a resounding yes and have brought the resulting game-changing products to market. As Dr Pat Brown, a renowned Stanford biochemistry Professor who left academia to found Impossible Foods, has noted, “the value proposition of meat has nothing to do with its coming from an animal.”


Food Production Despite the considerable history of plant-based meat on the market, the realm of this industry is still in its infancy. There are a wide variety of plant sources – not to mention less obvious but perhaps even more sustainable raw materials like fungi and algae – that remain completely unexplored for their suitability in plant-based meat. Nearly all plant-based meat products currently on the market are predominantly comprised of soy protein, wheat protein and more recently pea protein, but the vast majority of other high-protein crops have not been utilized in these applications. Likewise, only a single strain of fungal protein has been commercialized as a meat alternative. And while a few algal food ingredient companies exist, these source materials largely have not made their way into the plant-based meat industry. For any given source of this biomass, the subsequent processing stages must be tailored and optimized, and these processes are entirely within the biochemist’s domain. The first step is isolation or enrichment of the desired fraction (for example, to convert a pea flour that is 20% protein into a concentrate that is 80% protein). The second is functionalization, which includes chemical, biological and even mechanical methods for enhancing the ingredients’ performance in a plant-based meat formulation from the perspective of taste, texture and nutrition. The number of protein sources for which all of these methods have been optimized with plant-based meat in mind is abysmally small. The playing field is wide open for adapting these methods to new materials or for coming up with entirely novel and more innovative methods.

Cells, not animals, as the functional unit of meat There is always a degree of mimicry involved when making meat from plant-sourced proteins and fats that are unavoidably different from their animal-derived counterparts. The fidelity of plant-based meats – their ability to recapitulate the full sensory experience of meat, from the aroma on the grill to the burst of encapsulated fat in each bite – has improved dramatically in recent years. Yet, this endeavour fundamentally relies upon identifying a set of critical components or structures that must be reproduced, rather making a molecularly indistinguishable version of meat. But there is another approach whose aim is precisely that: building genuine animal meat without the animal. At its essence, meat is simply a collection of cells of various key types (muscle and fat are the most pertinent in mainstream cuts of meat) arranged in a matrix of connective tissue which contributes to the texture and structure of meat. Thanks to decades of animal cell culture


research for basic biological and biomedical applications, there exists a wealth of information for growing all of these cell types and tissue structures in vitro – outside the body of an animal. The basic process of clean meat production entails isolating a small number of cells from a donor animal. That starting population then expands exponentially through natural cell division, with the resulting cells seeded onto a 3D scaffolding material where the cells mature into the desired final cell types (muscle, fat and connective tissue). Biochemistry is critical to two main elements of the process: determining the nutrient composition of the cells’ feed and designing the scaffolding material. Within the nutrient feed, there are metabolizable energy sources (sugars, amino acids, fats), components that balance the salt and pH of the solution, and a small number of signalling molecules that trigger the cells to proliferate or transition into muscle or fat. All of these components must be optimized for each type of meat and cell line of interest. There is substantial potential to explore alternative components that perform better – for example, exhibiting higher stability in long-term culture or being more readily taken up by cells. The scaffolding material can be made of any edible, biocompatible material, such as a polysaccharide mesh that allows fluid and cells to migrate within it. Researchers have barely scratched the surface in terms of exploring biochemical modifications or linkages within the scaffold that could, for example, integrate flavouring components or cell signalling molecules. The clean meat industry is still relatively nascent, but the number of researchers, startup companies and investors who are committing their time and resources to this endeavour has boomed in the last 2 years. There are now over a dozen startup companies pursuing clean meat, and industry partners ranging from meat companies to life science companies are starting to get involved. While the idea of growing meat from cells is not new, there seems to be a global consensus that we just now have enough tools to begin to pursue clean meat in an earnest way. This is truly a pivotal moment for our food system, from many angles, and the fundamental principles of biochemistry underlie this paradigm shift.

Biology is a talented architect and builder The building blocks of biology are universal across all organisms: fatty acids, polysaccharides, amino acids and metabolites. The difference lies in the details: how they are arranged and the minute concentrations of subsets of molecules that serve as relatively unique fingerprints of a certain tissue type or class of organisms.

Food Production As a result, repositioning meat as simply one structural arrangement and formulation of these components allows us to reimagine the raw materials for making meat from a systems-level biochemical perspective.

Further reading

We can envision giving value to biomass that was once considered a by-product from other industries by converting it into the perfect feedstock for these alternative meats. While animals evolved to tolerate only a limited set of biomass as inputs, cells can utilize sugars, amino acids and lipids derived from any source. Likewise, the plantbased meat industry has already found clever ways of utilizing the protein fraction of crops that have historically been grown for components like starch or oil (for example, the oilseed crop soy) by structuring it into enticing meatlike textures. And it’s not just food and agriculture that have the potential to undergo a systemic efficiency reboot – there are opportunities to make use of side-streams from all sectors of the burgeoning bioeconomy including biofuels, biomaterials and industrial biotechnology. For example, companies like 3F Bio are utilizing nutrient-rich sidestreams from facilities like bioethanol refineries as a feedstock for high-quality protein, and some research groups are exploring modified plant cellulose – a byproduct from agriculture – as the basis for clean meat scaffolding. If the goal is ultimately a zero-waste system, one couldn’t hope for a more versatile set of fundamental building blocks than those that have evolved in biological systems.

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A call to action In recent years, the notion of rethinking meat has gained considerable traction among groups who are in a position to support this approach financially and politically. For example, high-fidelity meat alternatives promise governments a path towards domestic food security while meeting the growing protein demands of their population. Investors and the food industry recognize the financial opportunity posed by a substantially more efficient production method. Finally, philanthropic groups for causes ranging from public health to environmental responsibility see the merits of supporting a transition away from intensive animal agriculture. Increasingly, the bottleneck for accelerating the growth of the plant-based and clean meat industries is sourcing highly qualified technical talent. These companies are constantly seeking innovative scientists and engineers from a variety of backgrounds who possess a deep understanding of the fundamental biochemical nature of all cells, and therefore of all food. These are the creative minds driving technologies that challenge our notion of what meat is, how it can be produced, and how truly sustainable it can be – all while striving to satisfy consumers without sacrifice.

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UN Food and Agricultural Organization, World Livestock 2011: Livestock in Food Security. http:// www.fao.org/docrep/014/i2373e/i2373e.pdf Our World in Data, Global surface area allocation for food production. ourworldindata.org/wp-content/ uploads/2013/10/Land-use-graphic-01-01-01.png CB Insights (2017) Our meatless future: How the $90B global meat market gets disrupted. www.cbinsights. com/research/future-of-meat-industrial-farming/ Food Technology (January 2018). Is the Future of Meat Animal-Free? http://www.ift.org/~/media/food%20 technology/pdf/2018/01/0118_feat1_cleanmeat.pdf Specht, E.A., Welch, D.R., Rees Clayton, E.M. and Lagally, C.D. (2018) Opportunities for applying biomedical production and manufacturing methods to the development of the clean meat industry. Biochemical Engineering Journal 132, 161–168 The Good Food Institute (September 2017) Plant-based meat mind maps: An exploration of options, ideas, and industry. http://www.gfi.org/files/PBMap.pdf IEEE Spectrum (June 2018) The race to make a great fake steak. spectrum-ieee-org.cdn.ampproject. org/c/s/spectrum.ieee.org/green-tech/conservation/ the-race-to-make-a-great-fake-steak.amp.html The Guardian (April 2018) The new food: meet the startups racing to reinvent the meal. www. theguardian.com/environment/2018/apr/30/labgrown-meat-how-a-bunch-of-geeks-scared-the-meatindustry WIRED (February 2018) Lab-grow meat is coming, whether you like it or not. www.wired.com/story/ lab-grown-meat/ Fast Company (December 2017) Get ready for a meatless meat explosion, as big food gets on board. www.fastcompany.com/40508181/get-ready-for-ameatless-meat-explosion-as-big-food-gets-on-board

Liz Specht has a Bachelor’s degree in Chemical Engineering from Johns Hopkins University and a doctorate in Biological Sciences from UC San Diego. Her research in academia focused on synthetic biology to leverage living systems for high-impact applications in biomedicine, energy and global health. She joined The Good Food Institute (GFI) once she realized that one of the most pressing challenges facing our planet today – building a more sustainable, healthier and more humane food system – is fundamentally a biotechnology-addressable issue too. At the GFI she works with startups, academics, industry, and both public and private funders to accelerate the development and commercialization of alternatives to industrialized animal agriculture. Email: [email protected].


Food Production

RDA for microbes – are you getting your daily dose? Colin Hill (University College Cork, Ireland)

For almost all of human evolution our food and water has contained large numbers of microbes. Our immune systems evolved to cope with this daily intake, and our microbiomes (the collection of microbes on and in the human body) are increasingly recognized as playing an important role in human health. However, in recent times we have gone to great lengths to eliminate microbes from our diets, using food processing, water purification and hygiene to reduce our exposure. But has this come at a cost? Could our immune systems, primed to deal with trillions of microbes with every meal, be struggling to cope with their absence? Could this be a factor in the rise of modern inflammatory diseases in which the immune system misbehaves in response to dietary antigens or to our own epithelial cells? Perhaps we need to go back to consuming large numbers of (safe) microbes every day – a microbial RDA?

Throughout evolutionary history humans (and all other members of the Kingdom Animalia for that matter) would have encountered large numbers of microbes in the diet. Food and water collected from the environment by hunter-gatherers would inevitably have carried many bacteria, yeasts, moulds and viruses. The development of fermentation strategies for food preservation by our distant ancestors would also have ensured frequent ingestion of large numbers of safe microbes. It is also likely that our antecedents would not have been as particular in deciding when food was too spoiled to eat (early humans almost certainly did not observe ‘best-before’ instructions). It is difficult to guess at the numbers involved, but we could confidently expect our daily exposure to have been well in excess of 1010 microbes per day. Even the advent of cooking (approximately 2 million years ago) would not have significantly diminished the exposure to microbes in our diet. We can confidently expect that our immune systems, particularly the gut immune system, evolved to ‘expect’ daily exposure to large numbers of microbes. It is not surprising that a highly sophisticated immune system is located in the gastrointestinal tract with a vast array of receptors designed to recognize microbial molecules, and that our gastrointestinal immune system plays an important role in sifting out the beneficial or harmless food microbes from pathogens targeted for destruction. At some point in evolution we also discovered the benefits of drying, salting, sugaring and pickling our foods, while in more recent times the development of


effective food processing tools such as pasteurization and canning, refrigeration, freezing, aseptic packaging, food preservatives, water treatment and washing of fruit and vegetables before consumption has inevitably reduced our exposure to microbes. Of course, these more recent advances have happened in much too short a time for our immune systems to evolve and adapt to this significant reduction in microbial intake. It must be acknowledged and stressed that these food and water processing strategies have certainly reduced morbidity and mortality associated with food- and water-borne infections and thus form a vital role in protecting human health. I am not advocating a return to unhygienic food and water since this would be devastating to human health, particularly in a modern world where many people with compromised immune systems thankfully live long and productive lives. We do not want to return to an age where infectious disease claimed so many lives and only the ‘fittest’ or ‘fortunate’ survived into adulthood. But is it possible that these advances in food processing have come at a price in terms of losing our daily contact with dietary microbes? It is only in recent years that we have begun to appreciate the importance of our microbiomes – the vast array of microbes that live on and in the human body. Leaving aside the usual tropes of how we are more microbial than human in terms of cell count, we have come to appreciate that these commensal bacteria play important

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roles in our health. The evidence is compelling that these microbes influence health in many ways, including even a significant impact on mental health. In fact, over 10,000 papers were published in 2017 with ‘microbiome’ as a key word, emphasizing the current research effort devoted to this field. Our microbiomes are composed mainly of long-term resident or commensal bacteria we have accumulated over a lifetime, and the impact of dietary microbes is likely to be fleeting in comparison. But we should remember that most of our estimated 1014 resident gut microbes are located in the large intestine, whereas most of our immune cells (and those of our enteric nervous systems) are located in the small intestine. Thus, it is entirely feasible that dietary microbes arriving in the upper gastrointestinal tract could have a disproportionately larger impact on our immune system and enteric nervous systems than their relatively low numbers (in comparison with our microbiomes) would suggest. It is tempting to speculate that, in the absence of this daily influx of microbes, our underutilized immune systems could well be primed to react abnormally to other dietary antigens, or even to our commensal microbes. Could this play a role, however small, in the increased incidence of modern maladies such as food intolerances, low-grade inflammatory conditions and even atopic diseases (given our common mucosal immune system)?

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Probiotics, prebiotics and synbiotics Probiotics are safe living bacteria which have been shown to have a beneficial effect on human health. Several thousand human trials have been conducted with probiotics and the general consensus is that they can work well in certain health conditions, but the precise mechanism of action remain unknown for many probiotics. Prebiotics are ingredients (often complex carbohydrates) which cannot be digested by the human body, but are consumed by the bacteria living in the human gut. They are selective for certain groups of bacteria, and those which favour the growth of beneficial bacteria are considered to be prebiotic. Synbiotics are a combination of a prebiotic and a probiotic. In essence, the concept is that you provide both the beneficial bacteria (probiotic) and a selective food (prebiotic) which it can use in the gut, resulting in a synergistic effect (synbiotic).


Food Production

Is there any evidence to support the hypothesis that dietary microbes can benefit health? Yes, there is. In 1907 the Nobel Prize winning immunologist Ilya Metchnikoff published his treatise on longevity entitled “The Prolongation of Life: Optimistic Studies”. He proposed, on the basis of observation rather than experimentation, that Bulgarian peasants who ingested a large amount of fermented dairy products enjoyed long and healthy lives. He attributed this to the health benefits of the bacteria contained within yoghurt and other soured milks. This initial observation is usually credited as being responsible for the development of the probiotic concept which has grown into a multibillion Euro industry and has also been the basis of thousands of scientific papers. It is not difficult to find papers in excellent journals describing trials conducted to the highest standards (double-blinded, placebocontrolled) which demonstrate a range of health benefits for probiotics across immune conditions such as IBS (irritable bowel syndrome), ectopic diseases and even in anxiety, stress and cognition. One recent paper in Nature described a large randomly controlled trial involving over 4,500 Indian children which resulted in a highly significant reduction in sepsis following the consumption of a combination of a probiotic and a


prebiotic (an indigestible oligosaccharide which can only be metabolized by gut bacteria). The beneficial effect of probiotics is undeniable and scientists have worked hard to decipher the underlying mechanistic basis, but to date they have proven elusive. In fact, the broad range of health benefits associated with so many strains of probiotics has made many critical of the field, since if you assume a specific underlying mechanism for each health benefit, it seems unlikely that popular commercially available probiotics could have such wide ranging benefits. The broad range of benefits also seems improbable if you consider that most of the commercially available probiotics were selected decades ago on very simple criteria such as good growth rates in microbiological media, resistance to bile and an ability to survive gastric transit. However, if we consider that it may simply be the consumption of large numbers of safe bacteria that could confer a broad range of benefits then this may not be such a conundrum. This concept was featured in a recent consensus paper on the definition and scope of probiotics which referred to ‘core benefits’ of probiotic species – capturing the idea that the consumption of large number of almost any safe bacteria may have

Food Production broad ranging benefits, particularly in preserving health and in alleviating mild health problems. The same paper stressed that there are almost certainly individual probiotics that have more specific benefits, and so anyone choosing to take a probiotic because they suffer from a particular health issue would be well advised to look for strains or products with proven clinical evidence to support efficacy in those conditions. Nonetheless, the idea that consuming large numbers of safe bacteria is beneficial to preserving and even restoring health has some compelling supporting evidence. Consider a metaanalysis (one of many) conducted in 2012 which looked at 84 trials spanning 10,351 patients, 11 probiotic species or mixtures, and across eight gastrointestinal diseases. The authors concluded that “Across all diseases and probiotic species, positive significant effects of probiotics were observed for all age groups, single vs. multiple species, and treatment lengths”. Surely studies like this argue convincingly for the benefits of safe bacteria consumed in high levels in the diet. As an aside, it has always seemed odd to me that we accept without question the fact that the ingestion of a relatively tiny number of food-borne pathogens can have a massively disruptive effect on human health, even leading to death, but we are sceptical of the idea that the ingestion of much higher numbers of safe microbes could have any positive impact on human physiology. Perhaps even as scientists we instinctively subscribe to the idea that it is easy for a microbe to be bad, but much less likely for one to do good?

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So, how do we persuade a public brought up on the importance of hygiene, cleanliness and the prevailing message that the only good bug is a dead bug, to increase the numbers of microbes in their diets? Perhaps we could adapt the concept of an RDA (recommended dietary allowance) for microbes, taking advantage of the fact that this terminology is already familiar to consumers in the form of nutritional advice. The idea is simple; in addition to the existing RDAs for macronutrients, vitamins and trace elements, dietary guidelines should also advise consumers to deliberately include safe microbes in their daily diets. This should prove an easy message to convey and could be accomplished in a number of ways, but recommending increased consumption of fermented foods and the use of probiotics in food or in food supplements are two obvious solutions. What levels, and what microbes, I will leave to another day and/or to experts better able to consider this aspect, but I believe the microbial RDA concept is worthy of debate in a time of such high levels of chronic disease and gastrointestinal discomfort among so many individuals within society.

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Metchnikov, E. (1908) The prolongation of life: Optimistic studies www.gutenberg.org/ebooks/51521 Hill, C., Guarner, F., Reid, G., Gibson, G.R., Merenstein, D.J., Pot, B. et al. (2014) Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat. Rev. Gastroenterol. Hepatol. 11, 506–514 Panigrahi, P., Parida, S., Nanda, N.C., Satpathy, R., Pradhan, L., Chandel, D.S. et al. (2017) A randomized synbiotic trial to prevent sepsis among infants in rural India. Nature 548, 407–412 Ritchie, M.L. and Romanuk, T.N. (2012) A meta-analysis of probiotic efficacy for gastrointestinal diseases. PLoS One 7, e34938 Gibson, G.R., Hutkins, R., Sanders, M.E., Prescott, S.L., Reimer, R.A., Salminen, S.J. et al. (2017) Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat. Rev. Gastroenterol. Hepatol. 14, 491–502 Frei, R., Akdis, M. and O’Mahony, L. (2015) Prebiotics, probiotics, synbiotics, and the immune system: experimental data and clinical evidence. Curr. Opin. Gastroenterol. 31, 153–158 Quigley, E.M. and Shanahan, F. (2014) The future of probiotics for disorders of the brain-gut axis. Adv. Exp. Med. Biol. 817, 417–432 International Scientific Association of Probiotics and Prebiotics. isappscience.org/

Colin Hill has a PhD in molecular microbiology and is Professor in the School of Microbiology at University College Cork, Ireland. His main interests are in infectious disease, particularly in the role of the gut microbiome (bacteria and bacteriophage) in protecting against microbial infections in the gastrointestinal tract. He is also a Principal Investigator in APC Microbiome Ireland, a large Science Foundation Ireland supported research centre working with industry devoted to the study of the role of the gut microbiota in health and disease. In 2005 Professor Hill was awarded a DSc by the National University of Ireland in recognition of his contributions to research. In 2009 he was elected to the Royal Irish Academy and in 2010 he received the Metchnikoff Prize in Microbiology and was elected to the American Academy of Microbiology. He has published more than 500 papers and holds 18 patents. Email: [email protected]


Food Production

Starch: the best and worst of nutrients Fred Warren and Suzanne Harris (Quadram Institute, Norwich, UK)

The link between diet and health has been long known, as well as the fact that an increase in saturated fats and simple, refined carbohydrates in the diet, combined with our modern sedentary lifestyle, is contributing to an epidemic of diseases such as obesity and diet-related metabolic conditions. Although these can be multi-factorial disorders, simple lifestyle changes such as eating more fruit and vegetables in the diet and physical activity are known to be major factors in decreasing their prevalence. This has led to a focus on how dietary habits are affecting our overall health and how this information can be utilized to provide dietary solutions to combat the obesity epidemic. Of particular interest is the relationship between the digestion of starchy foods, which comprise 55 –75% of dietary energy intake, and the subsequent effects on health.

The availability of cooked starch is thought to have been crucial in providing the extra energy required by our brains during development from early to modern day humans. While the ability to improve the digestibility of starch through cooking, and thus access glucose to feed our growing brains, has been suggested to be key to the development of modern humans, it is now a major problem. We have become too adept at processing starchy foods to maximize starch digestibility.

Starch digestion Starch digestion begins the moment you bite the cookie, with the oral release of salivary α-amylase (the enzyme in our digestive tract that breaks down starch to sugars) as well as mechanical shearing when the food is chewed and swallowed, enzymic breakdown is slowed in the stomach by low pH and started again in the duodenum with the release of pancreatic α-amylase. The nutritional properties of starch are reliant on its digestibility and not all starch is created equal. Starch differs depending on source, structure and processing, as well as intrinsic factors including granule size and arrangement and the amylose-to-amylopectin ratio (high amylose starches tend to be more resistant to digestion). Historically, it was thought that all starch was rapidly digested in the upper digestive tract to simple sugars, or monosaccharides, but research in the 70s and 80s demonstrated that some starch is much more slowly digested or completely resistant to digestion.


Physical chemistry in the kitchen Currently, we are learning more about the links between starch structure at the molecular level and its digestion. Raw starch has a complex crystalline structure that reduces the accessibility of α-amylase to the chains of glucose which make up the starch molecule. This limits the ability of the enzyme to digest the starch, hence, the effectiveness of cooking for increasing digestibility. In some cases (for example, bananas), we do eat starch in its raw form, but we generally want to cook food before eating it. Research suggests several ways that the physical structure of cooked starch can be influenced to control its digestion. The simplest approaches to manipulate starch molecular structure, which we can do in our own kitchen, involve simply cooling food after cooking. Starch comprises two different glucose polymers, amylose and amylopectin, amylose being a linear polymer, and amylopectin being highly branched, like a tree. In raw starch, these polymers are packed into a semi-crystalline granule, but following cooking the crystallinity is disrupted, and the polymers are released. When starch is cooled after cooking, the amylose rapidly recrystallizes, within 30–60 minutes. The crystalline structure formed is inaccessible to digestive enzymes, and thus resists digestion. The branching of the amylopectin causes recrystallization to occur far more slowly, over several days. This process leads, for example, to bread going stale. The short, branched chains of amylopectin form far less stable crystalline structures than the long amylose chains. Thus, when we reheat cooled food the amylopectin crystals melt (at around 60°C), whereas the amylose crystals, with a far higher melting point (around 120°C), remain stable. Therefore,

Food Production by cooling and reheating starch-containing foods, we can retain the crystallized amylose, which is highly resistant to digestion, while maintain the texture of the food through melting the amylopectin crystals. This effect has been understood since the work of Berry and others in the 1980s, but it is only recently that it has become more widely acknowledged in dietary advice.

High-tech starches While there are simple methods that can be used in the kitchen, there are also more advanced technological approaches to reducing the digestibility of starches. One option is to alter the processing parameters of staple foods, such as biscuits, in order to render starch less accessible to digestive enzymes. This can be achieved through an understanding of the factors which control the loss of crystallinity during starch cooking. The key factors are moisture and temperature, with the temperature required to melt starch crystals being dependent on the amount of water available during cooking. Some food manufacturers therefore use a combination of low moisture, low temperature cooking to control starch crystallinity, and therefore digestibility, but this is only possible in a narrow range of products. An alternative strategy is the use of advanced plant breeding methods to produce starches with structures which are inherently resistant to digestion, either through increasing the melting temperature of the starch, or increasing the amount of amylose that can recrystallize following cooking and cooling. Starch biosynthesis is a complex process involving enzymes which catalyse chain elongation, chain branching and chain debranching, with several isoforms of each enzyme required to synthesize

a starch granule. By using targeted genetic approaches, plant breeders are able to knock-out specific isoforms of starch-branching enzymes in common crops such as wheat and pea. Using this approach, in the future it will be possible to breed crops with starches which are inherently resistant to digestion.

Into the colon When we eat food, it spends around 5–30 seconds in the mouth, during which time it is chewed and mixed with salivary amylase, initiating starch digestion. After swallowing, the food then spends around 30 minutes to an hour in the stomach. Although the environment of the stomach is highly acid, the buffering effect of the food is such that starch digestion continues in the stomach, before the food then moves into the small intestine. Here, it mixes with pancreatic amylase and the starch is further digested to maltose and highly branched dextrins, which are degraded to glucose by enzymes in the brush border of the small intestine and adsorbed. Foods take around 2 hours to pass through the small intestine. Given this time limitation, any starch which is so slowly digested that its digestion is not fully complete after this 3-hour process will pass into the colon. The colon is home to trillions of bacteria, from between 400 and 800 different species, many of which are evolved to degrade highly crystalline forms of starch. The bacteria in our colon ferment starch to produce short chain fatty acids (SCFAs), which are absorbed by the host (that’s us) and which helps recover energy from our diet, but also provide a range of other potential health benefits. The most abundant SCFAs, acetate, propionate and butyrate (which together comprise around 95% of all SCFAs

Figure 1. The molecules produced by bacterial fermentation of starches can directly signal to our brains


Food Production Figure 2. Gut bacteria can affect decisions including what we want for dinner.

in the colon), have been linked with multiple benefits, including providing dietary energy and suppressing the growth of pathogens by decreasing the pH of the intestinal lumen. Acetate has a major role in the ability of beneficial Bifidobacteria to inhibit toxicity from gut pathogens by blocking the transport of toxins from the gut lumen to the blood. Propionate can help to lower cholesterol levels by inhibiting the synthesis and reuptake of LDL cholesterol. Butyrate is the preferred energy substrate for the colonic epithelium. Butyrate has been linked with protection from initiation of colon cancer by many different pathways including promoting cell differentiation, cell-cycle arrest and apoptosis of transformed colonocytes. Besides digestion and fermentation, the interaction between starchy food and the gut microbiota has recently been found to be important in sending and receiving signals from the brain, known as the gut–brain axis. Changes to the composition of gut bacteria and


subsequent changes to the release of SCFAs as signalling molecules can have great effects in the body, from influencing mood and behaviour to altering immune responses. For example, SCFAs can activate the free fatty acid receptor FFAR3, which then activates a signalling cascade. This signalling can result in changes to intestinal immunity by mediating inflammatory responses by gut immune cells, acting to reduce inflammation and protect the gut lining. These signals can also have wider effects on energy homeostasis and appetite, signalling to our brains that we feel full (Figure 1). In regulation of the appetite, the composition of our gut microbiota can be very important – some microbes produce metabolites small enough to pass through the blood–brain barrier during fermentation, including the amino acids tryptophan and tyrosine. These amino acids are converted into the neurotransmitters serotonin and dopamine, providing a mood-boosting reward for the

Food Production host when these bacteria have been fed (Figure 2). Diet is the most important factor in shaping the gut ecosystem, which has profound effects on not just our digestive heath, but all areas of the body. Starch is the single largest component in the human diet. Therefore, research on the effects of starch structure and how modifications alter its digestibility can have a far-reaching impact on our health.

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Fred Warren is a Career Track Research Leader at the Quadram Institute in Norwich, where he leads a research group focussing on unravelling the links between starch molecular structure, starch crystallinity and starch digestion. Working from crop science to colon models he aims to understand how this fascinating molecule is synthesized, how it is structured, and how it is broken down. Email: [email protected]

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Berry, C.S. (1986) Resistant starch: formation and measurement of starch that survives exhaustive digestion with amylolytic enzymes during the determination of dietary fibre. J Cereal Sci 4.4, 301–314. Blaut, M. (2002) Relationship of prebiotics and food to intestinal microflora. Eur J Nutr 41, 11–16 Edwards, C.H., Warren, F.J., Milligan, P.J., Butterworth, P.J. & Ellis, P.R. (2014) A novel method for classifying starch digestion by modelling the amylolysis of plant foods using first-order enzyme kinetic principles. Food Function 5, 2751–2758 Englyst, H.N. & Cummings, J.H. (1987) Resistant starch, a ‘new’ food component: a classification of starch for nutritional purposes. In: Cereals in a European Context (Morin, I.D., ed.), pp. 221–233 (Ellis Horwood, Chichester) Ritzhaupt, A., Ellis, A., Hosie, K.B. and Shirazi‐Beechey, S.P. (1998) The characterization of butyrate transport across pig and human colonic luminal membrane. J Physiol 507, 819–830 World Health Organization (2003) Diet, Nutrition and the Prevention of Chronic Diseases. Report of a Joint WHO/FAO Expert Consultation (WHO Technical Report Series 916) Williams, E.A., Coxhead, J.M. & Mathers, J.C. (2003) Anti-cancer effects of butyrate: use of micro-array technology to investigate mechanisms. Proc Nutr Soc 62, 107–115 Wolever, T.M., Spadafora, P. & Eshuis, H. (1991) Interaction between colonic acetate and propionate in humans. Am J Clin Nutr 53, 681–687


Lifelong Learning

Synthetic Biology Public Engagement Corinne Hanlon (University of Warwick, UK)

The Warwick Integrative Synthetic Biology Centre (WISB) spent an amazing week interacting with visitors of all ages at the Cheltenham Science Festival from 5–10 June 2018.

After months of development, including liaising with artists in Central Saint Martin’s through the Biochemical Society’s Art Science Exchange project, WISB unleashed their giant E. coli and SynBio virtual reality experience on school children and the general public, and were delighted with the reception to both activities. For such a rapidly developing field, there is relatively little coverage of SynBio in the mainstream media. The aim of WISB’s engagement was simple and twofold: First, to inform school children and the general public that one of the technologies used in SynBio can be described as reprogramming DNA,

WISB at the Cheltenham science Festival, 5–8 June 2018

30 August 2018 © Biochemical Society

in this case via CRISPR, and that CRISPR can be described as a molecular ‘cut and paste’ tool. Second, that the genetic material in living cells can be redesigned and reconstructed in a manner analogous to an electrical circuit. To explain how DNA can be reprogrammed, visitors opened up the giant, furry E. coli and worked inside of it to reprogram the operation of a light bulb using various logic gates such as AND, OR, NOR and XOR. This was linked to the SynBio AND logic gate which controls the expression of a gene encoding the green fluorescent protein (the input signals arabinose AND salicylate are required to switch this on). The SynBio virtual reality experience, entitled “An Introduction to Synthetic Biology”, allowed visitors to take on the role of CRISPR and to perform a ‘cut, copy and paste’ of their own. Visitors started the experience on a regular suburban street which became saturated with strands of DNA once dusk falls. Visitors were instructed to grab a tiny scalpel (more like a lightsaber!) in order to make an incision in a giant strand of DNA. After picking up a new gene of their choice, the visitor inserted this into the incision, and activate expression of the inserted gene. Upon activation, the visitor returned to the regular suburban street to see a colossal change: all of the trees are glowing. This virtual reality experience allowed the general public to see what could happen if fluorescent proteins were successfully expressed in plants. A scenario is presented to the visitor that we could perhaps oneday use advances such as this to help reduce our reliance on fossil fuels or to perhaps help reduce starvation and malnourishment by increasing the shelf-life of food.

Lifelong Learning There were over 7,000 school children and staff in attendance between Tuesday 5 and Friday 8 June, with numbers for the weekend not yet available. WISB were able to collate feedback from 500 visitors, 85% of whom were under 20 years of age. Overall, a fantastic 97% of respondents felt that attending the WISB stand increased their awareness of SynBio and we are delighted that 96% of our 500 respondents claimed that they now wanted to know more about SynBio. Based in the University of Warwick, WISB is one of six BBSRC/EPSRC-funded UK Synthetic Biology Research Centres and is led by Professor John McCarthy. We deliver an internationally leading programme of integrated research, innovation and training for synthetic biology. WISB’s unique combination of enabling research, industrial collaboration and training will underpin the future development of synthetic biology whilst delivering innovative solutions to challenges in biotechnology, medicine, food security and the environment, and will confer significant opportunities for societal and industrial impact. Delivered in collaboration with international partners, WISB’s five integrated research themes address specific, industrially relevant design challenges across the scales of biological organization: molecular interactions, genetic circuits, pathways, and multicellular systems. WISB is grateful for the additional funding for this public engagement project which came from the University of Warwick’s Faculty of Science, the Institute of Advanced Study, the School of Life Sciences and the Wellcome-Warwick Quantitative Biomedicine Programme. Additional funding was also received from the Biochemical Society’s Scientific Outreach Grant and sponsorship from Snap Circuits.

Visitors try out the VR experience

For more information on WISB’s public engagement activities, please contact Dr Corinne Hanlon ([email protected]). You can see a trailer of the VR experience here youtu.be/XgwznSSULk8 and the full VR experience here youtu.be/Uhl6R1QJr2Q.

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Snap circuits are used to model SynBio pathways


Science Communication Competition

About cats, mice and behaviour-changing parasites Victoria Bolton (University of Glasgow, UK)

The Science Communication Competition is now in its eighth year. As in previous years, it aims to find young talented science writers and give them the opportunity to have their work published in The Biochemist. In 2015, a new branch of the competition was launched to include video entries. Overall this year’s competition attracted 74 entries and these were reviewed by our external panel of expert judges. The first prize in the written category was awarded to Victoria Bolton from the University of Glasgow, whose article is presented here; the winner of the video category was Jirayu Tanprasertsuk from Tufts University. Jirayu’s winning video can be viewed at bit.ly/scicommvid2018.

One day, Jerry the small and clever mouse from the cartoon series “Tom and Jerry” stopped outsmarting the cat, Tom. Instead, Jerry no longer felt that Tom was his enemy. He felt an irresistible attraction towards Tom and how he smelt. Shortly after, Tom took his chance. Jerry ended up on Tom’s plate, seasoned with salt and pepper and topped with mint sauce. Tom had Jerry for supper and lived happily ever after. THE END. Imagine this was the end to an episode of “Tom and Jerry”. That’s the moment when you would probably say: “What is happening? Something is up!” And you would be right. Something is up. Jerry is infected with a mind-controlling parasite called Toxoplasma gondii.

But what is Toxoplasma gondii? And how did Jerry become infected? Toxoplasma gondii is a small parasite, about 40–400 times smaller than a small grain of sand. It can live in cells of any warm-blooded animal like a mouse, rabbit, your pet cat or us humans. Toxoplasma’s journey into Jerry begins in the gut of a cat like Tom, who is infected with Toxoplasma gondii. Tom, the cat and any other catlike animal (e.g. tiger) are Toxoplasma’s definitive host. This means Tom is Toxoplasma’s home base: the place it must always come back to. Tom, the cat, sheds small, round structures called oocysts in his stool. These structures have a very thick and protective wall, which protects them from extreme conditions in the outside world, just like the walls of your house protects you from the cold in winter. Like this, the oocysts can stay in the environment for a long time and mature.

Figure 1. Toxoplasma oocytes are shed in cat faeces Image of the oocyst is taken from fwfx.info/toxoplasma-gondii-egg.html


Science Communication Competition Jerry, or any other mice and small animals which cats feed on, are intermediate hosts. This means that they are a temporary home or place Toxoplasma visits and needs for its personal development, as it cannot stay at home all the time. Intermediate hosts like Jerry become infected because they accidentally take up Toxoplasma’s mature oocysts with their food. After Jerry has consumed these small, round structures, they change their form to adapt to their new environment. It’s very much like when you come in from outside on a winter’s day wearing a thick jacket and enter a well-heated room. You change or undress as you do not need the thick warm clothes inside. Similarly, once inside, Toxoplasma gets rid of the structure with the thick protective wall; it changes into a small, dropshaped structure called a tachyzoite. Toxoplasma now has a mission. In order to thrive and survive, the parasite needs to get inside a cell. Sadly, for Toxoplasma, cells have a barrier around them called the ‘cell membrane’ that protects them like a wall around a castle. Luckily, its new form – the tachyzoites – possess small sacks and structures called micronemes, dense granules and rhoptries inside, which contain molecules that help the parasite to move, invade and survive once inside the cell. These molecules are Toxoplasma’s personal set of aces up its sleeves, which it can shake out to win whenever they are needed. Using some of these, tachyzoites can form a machinery called a glideosome that acts like a motor with which they can glide along the surface of the cell like a tank. With the force generated by the glideosome and some extra help of more Toxoplasma molecules, called AMA-1 and RON, which form a hoop called a moving junction, the parasite moves forward, front end first through the hoop and invades the cell. Toxoplasma then multiplies and lives happily inside the cell. All very easy, Toxoplasma, right? Well…Jerry’s immune system does not like to see this invader. It activates its alarm bells and sends its defence army of killer T-cells, whose function it is to sacrifice the infected cells and kill Toxoplasma. Since Jerry’s army of defending cells sets out to kill, Toxoplasma chooses to withdraw from the battlefield. It creates small structures, called tissue cysts or bradyzoites where it can hide in the muscle or brain. The brain is a special site. Not only because it is the control centre of our body, but also because most immune cells (cells that defend our body from ‘invaders’ like Toxoplasma) have restricted access to the brain. Thus, by hiding in the brain, Toxoplasma makes another smart move as most immune cells will not come looking for the parasite there. It’s like laying low in a place with little surveillance, not creating too much uproar after you robbed a bank to avoid the attention of the police.

Figure 2. Parasite invasion into cells involves many parasite-secreted proteins

What happens next on Toxoplasma’s journey is very interesting. Mice like Jerry who have been infected for a while with Toxoplasma change their behaviour. Any other mouse would avoid cats like Tom and their smell. In contrast, Jerry, who is infected with Toxoplasma does not avoid Tom or Tom’s smell, but instead becomes attracted to the scent. Jerry even develops an interest in sniffing Tom’s pee (oh dear). This makes Jerry an easy meal for a cat like Tom.

But how does Toxoplasma make Jerry act like that? The exact mechanism of how Toxoplasma changes Jerry’s behaviour remains to this day unknown, but there are several possible explanations: One explanation is that Jerry’s behaviour could be changed because Toxoplasma forms cysts in the brain areas that control Jerry’s feelings of fear, his senses and his decision making. That way, Toxoplasma could simply mix up their normal function, just like an uninvited, hostile intruder into a headquarter or the parliament would. The outcome being Jerry losing his fear of Tom and his smell. Another possibility is that some of Toxoplasma’s molecules are involved in changing Jerry’s behaviour. Two molecules of Toxoplasma, called AAH1 and AAH2, are very similar to a human molecule that is involved in making dopamine. Dopamine is a chemical August 2018 © Biochemical Society 33

Science Communication Competition that can be found in our brain and is involved in the creation of ‘reward’ and ‘pleasure’ feelings. One could say that dopamine is the molecule of lust, motivation and addiction. By producing molecules that are similar to those involved in making more of the chemical dopamine, Toxoplasma may increase dopamine levels in Jerry’s brain, thereby changing Jerry’s behaviour in a way that he is attracted instead of repelled by the smell of Tom. Indeed, scientists have found that the areas around the structures Toxoplasma forms in the brain contain a lot of dopamine. A third possibility involves the male sexual hormone testosterone, a hormone responsible for sexual and risky behaviour. It is the hormone that changes your calm husband, friend, boyfriend or brother into a roaring Neanderthal who thinks he can take it up with the whole world during a Sunday football match. This hormone has been found at increased levels in male rats infected with Toxoplasma. Thus, as a result of increased testosterone levels in his blood, Jerry may become more daring and think he can take it on with a cat. Moreover, since testosterone increases sexual behaviour, Jerry even may become attracted by the cat’s smell, like he would be attracted by a charming mouse lady. By whatever mechanism Toxoplasma changes Jerry’s behaviour, Jerry ends up as Tom’s supper. Jerry’s demise is good for Toxoplasma, because Jerry was just a temporary home for Toxoplasma and it needs to get back to its definitive host: the cat, Tom. The eternal cycle of cats, mice and mind-controlling parasites is completed.

Does Toxoplasma also change human behaviour? But Toxoplasma is not only a parasite of mice and cats but can also infect us humans. In fact, one in three people worldwide are infected with this parasite. Humans become infected by the consumption of undercooked meat of an infected animal or food or water that has become contaminated with cat faeces. Since we are unlikely to be the meal of a cat or tiger (unless we are the adventurous type on a jungle safari), Toxoplasma lives within us inactivated as cysts in the muscle, heart, brain or eyes. Does that mean we have a preference for cat urine now? Not necessarily. Some studies suggest that the parasite increases jealousy and the tendency to disrespect rules, while others point out a link between Toxoplasma infection and schizophrenia. Although you may think now that your jealousy is the result of ‘advanced’ parasite-mediated mind control, most studies have studied correlation, not cause-effect, limiting the extent to which we can conclude if the parasite changes our human behaviour. So, no reason to worry. Nevertheless, Toxoplasma infection can have serious consequences: in pregnant women that become infected for the first time, Toxoplasma can be transferred from the mother to the unborn baby where it can cause serious birth defects. While Jerry sadly cannot be saved, if you are not yet infected and you are planning to have a baby, you can minimise the risk of becoming infected by simple means like cooking your meat properly and washing your hands, fruits and vegetables.

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Further reading • • • • • • • • • • • • •

Dubey, J.P. (1998) Advances in the life cycle of Toxoplasma gondii. Int. J Parasitol. 28, 1019–1024 Dumètre, A., Dubey, J.P., Ferguson, D., Bongrand, P. Azas, N. and Puech, P. (2013) Mechanics of the Toxoplasma gondii oocyst wall. Proc. Natl. Acad. Sci. 110, 11535–11540 Centers for Disease Control and Prevention (2015) Toxoplasma life cycle. Available at www.cdc.gov/parasites/toxoplasmosis/biology.html Mercier, C. and Cesbron-Delauw, M. (2015) Toxoplasma secretory granules: one population or more? Trends Parasitol. 31, 60–71 Keeley, A. and Soldati, D (2004) The glideosome: a molecular machine powering motility and host-cell invasion by Apicomplexa. Trends Cell Biol. 14, 528–532 Carruthers, V. and Boothroyd, J.C. (2007) Pulling together: an integrated model of Toxoplasma cell invasion. Curr. Opin. Microbiol. 10, 83–89 Filisetti, D. and Ermanno, C. (2004) Immune response to Toxoplasma gondii. Annali dell’Istituto superiore di sanita 40, 71–80 Pachter, J.S, De Vries, H.E. and Fabry, Z. (2003) The blood brain barrier and its role in immune privilege in the central nervous system. J. Neuropathol. Exp. Neurol. 62, 593–604 Webster, J.P. (2007) The effect of Toxoplasma gondii on animal behavior: playing cat and mouse. Schizophrenia Bulletin 33, 752–756 Vyas, A., Kim, S, Giacomii, N., Boothroyd, J. and Salpolsky, R. (2007) Behavioral changes induced by Toxoplasma infection of rodents are highly specific to aversion of cat odors. Proc. Natl. Acad. Sci. 104, 6442–6447 Gatkowska, J., Wieczorek, M., Dziadek, B., Dzitko, K. and Dlugonska, H. (2012) Behavioral changes in mice caused by Toxoplasma gondii invasion of brain. Parasitol. Res. 111, 53–58 Vyas, A. (2015) Mechanisms of host behavioral change in Toxoplasma gondii rodent association. PLoS Pathogens 11, e1004935. Flegr, J. (2013) Influence of latent Toxoplasma infection on human personality, physiology and morphology: pros and cons of the Toxoplasma–human model in studying the manipulation hypothesis. J. Exp. Biol. 216, 127–133


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Careers

A day in the life of a Policy Officer Tom Livermore is a Senior Policy Officer at the Academy of Medical Sciences and has been working there since early 2017. Tom studied Natural Sciences at Cambridge before specializing in Biochemistry and then undertook an MRC-funded PhD in Biochemistry at UCL. While completing his PhD, Tom completed a 3-month internship at the Association of Medical Research Charities. His first full-time policy role was at the Royal Society of Biology. Peter Wotherspoon (Training & Careers Intern, Biochemical Society) spoke to him about his work. How did you get into science? I can’t pinpoint the moment I got into science. I wasn’t one of those kids who had a chemistry set from the earliest age, but when it came to applying to university there was never any doubt. I studied Natural Sciences, ultimately specializing in biochemistry, but after that it was more through luck than judgement that I spent a thoroughly enjoyable 4 years in the lab completing my PhD. One of the things that I learnt during my PhD was that science is actually an incredibly creative process and it is this that I will miss most now that I have left the lab. What is your advice for someone who would like to pursue a career in policy making? My best advice is to get out there and try things. Whether it is writing things for your school, university or local paper; getting involved in student think tanks; or taking time out to do an internship or policy fellowship, there are many ways to explore

the topics you find interesting about how policy and science interact. I would never have known what science policy is all about if I hadn’t tried it. What’s the most interesting project you’ve worked on? Currently I work on very a broad range of topics, from advocating for public investment in research to understanding how medical research will be affected by leaving the EU. I find this variety both extremely interesting and challenging. Possibly, the most inspiring project I have worked on, however, was during my first experience of policy and public affairs. During an internship taken midway through my PhD, I was extremely lucky to work on the mitochondrial donation regulations as they made their way through Parliament. I can’t claim any credit whatsoever for the passage of those regulations, but as an observer, seeing the work that went into securing the legislative change that enabled real people to benefit from life-changing research was a huge privilege.

CAREERS IN MOLECULAR BIOSCIENCE

TEACHING

FOOD INDUSTRY


THE COSMETIC INDUSTRY

PHARMACEUTICAL LABORATORIES

PUBLISHING

SALES AND MARKETING

Careers

What inspires you about your job? I’m lucky to work with some extremely inspiring people, both colleagues and researchers. The Academy’s work is informed by the expertise of our Fellowship, which is comprised of some of the best clinical and biomedical researchers in the UK. Tapping in to their collective expertise and using that to promote biomedical research with the aim of translating this into benefits for society is an inspiring goal. What’s been the greatest challenge in your career so far? One of the biggest challenges of a career in policy is also one of the main attractions; you have to be ready for anything. You can never quite predict what you’ll be faced with from one day to the next (I’m thinking of the snap general election in 2017), but you have to be ready when it comes. That means that you have to be quick to react, able to digest complex information at speed and then able to respond rapidly.

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For more information on the Biochemical Society’s policy activities, visit www.biochemistry.org/Sciencepolicy

RESEARCH

LAW FIRMS

Job profile Policy officers concern themselves with reviewing, developing and communicating the guiding principles of public and private sector organizations. This involves investigating the impact of changing government legislation, identifying areas of improvement in existing policies, conveying changing policies and informing new policies. Responsibilities Responsibilities include attending meeting and events, communicating internally within their organization and externally to inform policy through round tables, discussions and responding to organizational and government inquiries. Policy Officers research and respond to current events and of course developing policy and strategy for the betterment of their organization. Qualifications Policy Officers come from a variety of backgrounds ranging across the science, arts and humanities dependant on sector. Ultimately, Policy Officers must have a detailed and in-depth knowledge and understanding of the policy issues that affect their sector, and possess the skills to research, develop and articulate policy. Undergraduate and postgraduate qualifications in policy analysis and development are available to those interested, but qualified scientists can also pursue a career in policy. Salary and career development The salary for newly qualified policy officers ranges from £20,000 to £25,000 which rises to upward of £30,000 after some years of experience. Policy professionals often move to work for larger and further-reaching organizations that deliver policies affecting a wider range of areas and people.

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POLICY August 2018 © Biochemical Society 37

Policy Matters

Evidence, engagement and informed policy making Emma Sykes (Science Policy Officer, Biochemical Society)

June 2018 saw the successful launch of the UK’s first Evidence Week, a collaboration between Sense About Science, The House of Commons Library, and the Parliamentary Office of Science and Technology (POST). A week-long event filled to bursting with high-profile speakers, workshops and roundtable discussions, Evidence Week highlighted the importance of evidence-based policy making in the heart of Parliament. Members of both Houses couldn’t escape the stands, the banners and the Voice of Young Science Network who were enthusiastically sharing the importance of evidence against a broad backdrop of issues ranging from solving the UK housing crisis to regulating genome editing.

With the very nature of science being underpinned by the generation and analysis of evidence, it is sometimes difficult for scientists to understand why policies do not always seem to follow the direction of available scientific evidence. Indeed, there are many other factors that come into play in policy making, including social, political and economic factors, and often these can appear to outweigh available scientific evidence when policies are agreed. For example, the cost-effectiveness of new medicines available on


the NHS or the strict regulations regarding genome editing. However, it is important that MPs are wellversed in the importance of informed policy making and it is imperative that policies are based on robust data and good-quality evidence, whether that be scientific or economic. As Chair of the House of Commons Science and Technology Committee, Rt Hon Norman Lamb MP, said at the evening launch of Evidence Week “If you make policy without applying evidence, ultimately you don’t achieve your objectives”.

Policy Matters

Evidence Week opened a dialogue between parliamentarians and the scientific community and showed that, despite popular belief, we are not living in a post-truth era. Evidence very much underpins many of the decisions made by Government and we must hope that it continues to do so. However, in order to ensure that policy decisions are based on high-quality evidence, scientists must maintain this dialogue and continue to engage and communicate their research and expertise to the public, parliamentarians and policy-makers. One of the main barriers for scientists in engaging with policy is often a lack of confidence, both in terms of their own relevant expertise and general uncertainty in how they can get involved. Policy making can be seen as an unfathomable maze with no obvious way in, but the reality is, anyone can engage with policy and it can be as simple as writing a blog or inviting your local MP to your lab to share your work. Engaging with your relevant Learned Society can be an easy way to understand more about policy and ways to become involved. Many Societies represent their communities to Government and Parliamentary Committees through events, roundtables and responding to consultation inquiries. Researchers can also attend and participate in numerous events that expose them to policy makers, such as Voice of the Future, Parliamentary Links Day and STEM for Britain, where early-career scientists present their research in the Houses of Parliament. To further support our members, the Biochemical Society also has an informal Policy Network. This is an online group of members who have indicated their interest in

policy and wish to stay up-to-date with the Society’s policy work. Network members can comment on consultation responses, learn about policy events and stay up-to-date with key policy issues affecting the molecular bioscience community through the quarterly newsletter.

Photography: James Hopkirk

MPs cannot be expected to know about all aspects of science, or every area that impacts society or the economy. As experts in their field, it is important that scientists engage with policy and are able to communicate their research in an understandable and accessible way. Informed policy making requires more than just the available scientific evidence. It is also vital that there is an open dialogue between scientists and policy-makers, where both sides can share their expertise against a back-drop of mutual understanding and respect.

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Further Reading: •

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The Biochemist Blog No Weak Evidence! It’s Evidence Week! (Leah Fitzsimmons) www.thebiochemistblog. com/category/blog-posts/policy/ Sense About Science Voice of Young Science Network http://senseaboutscience.org/voys/ POST Evidence Week: Why scrutinising evidence matters www.parliament.uk/mps-lords-and-offices/ offices/bicameral/post/post-events/evidence-week/ The Guardian Commons people: why parliament’s ‘evidence week’ is a national victory: www.theguardian. com/politics/2018/jun/25/commons-people-whyparliaments-evidence-week-is-a-national-victory


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News

Upcoming Events Protein Disulphide Bonds: Biochemistry, Biotechnology and Biomedical Impact 31 August–1 September 2018, Kent, UK

Meeting Reports 2018 British Meiosis Meeting 24–25 May 2018, Brighton, UK

Biennial International LRRK2 Meeting 2–4 September 2018, Padua, Italy 84th Harden Conference: Single-molecule Bacteriology 9–12 September 2018, Oxford, UK Acylation of Intracellular and Secreted Proteins: Mechanisms and Functional Outcomes 10–12 September 2018, Brighton, UK R for Biochemists 101 10 September 2018 online course The Changing Landscape of Research on Ageing: Models, Mechanisms and Therapies 7 November 2018, Glasgow, UK Synthetic Biology UK 2018 19–20 November 2018, Bristol, UK

This year marked the 10th anniversary of the British Meiosis Meeting, with a strong focus on presentations from junior group leaders, postdocs and PhD students. This year we were particularly fortunate to have a number of international PIs in the audience, and it was a pleasure to observe them interacting with PhD students and postdocs, as well as the brave few presenting a poster! The meeting was split broadly into four oral sessions covering aspects of genetic recombination, crossover formation, chromosome structure and segregation. The first and third session were opened with engaging invited talks (sponsored by the Biochemical Society) from Professor Scott Keeney and Professor Eva Hoffmann who presented recent progress on

their studies of meiosis in mammals. As well as 15 selected talks, the meeting also included 43 outstanding posters, generating a lot of useful interaction opportunities. Highlights from the meeting (prize winners) were two excellent analyses of chromosome structure in yeast and mouse meiosis using, respectively, HiC (Stephi Schalbetter, Neale lab), and FISHbased microscopy (Isobel MacGregor, Adams lab), and Laura Gomez Hernandez’s detailed study of SIX6OS1, a novel component of the synaptonemal complex (Pendaz lab). Overall, the atmosphere of the meeting was very friendly with many discussions. Matt Neale (University of Sussex, UK)

The Biology and Physics of Bacterial Chromosome Organisation 2018 4–6 June 2018, Leiden, The Netherlands

Life Sciences 2019: Post-translational Modifications and Cell Signalling 17–18 March 2019, EMCC, Nottingham, UK BMP Signalling in Cancer II 1–April 2019, St Anne’s College, Oxford, UK Redox Signalling in Physiology, Ageing and Disease 1–3 July 2019, Newcastle, UK Protein Engineering II: from New Molecules to New Processes 15–17 July 2019, University of York, UK 9th European Conference on Tetraspanins 4–6 September 2019, Schloß Waldhausen, Budenheim, Germany

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The meeting was focused on understanding the principles that control folding of bacterial chromosomes in the context of whole cell biology, transcription and DNA replication, and welcomed delegates from ten different countries. Exciting new research highlights included insights from superresolution microscopy showing that the folding chromosome adopts a ‘doughnut’like structure, real-time visualization of DNA loop extrusion by SMC proteins, and insights into the way that transcription can play a dominant role in controlling

chromosome configuration. Attendees also had a private tour of the Boerhaave Museum, the Netherlands’ treasure chamber of science and medicine, with a collection spanning five centuries of research and innovation. A key takeaway message was that integrating novel new approaches is key to advancing this area of research. David Grainger (University of Birmingham, UK) Remus Dame (University of Leiden, The Netherlands) Olivier Espeli (College de France, France) Paul Wiggins (University of Washington, USA)

News

Local Ambassador – Maddy Parsons Maddy is Professor of Cell Biology within the Randall Centre for Cell and Molecular Biophysics at King’s College London. Her research team use biochemical and advanced microscopy approaches to investigate how cells use signalling proteins to sense and respond to their environment. What motivated you to become a scientist? I had a brilliant GCSE biology teacher – she was very smart, very cool and got me really interested in the mysteries of cells. And she made me realise science wasn’t just for geeks (ironically I’m sure I actually now fall firmly into that category). I was actually much better at languages and history than science at school so I think everyone was as bit surprised (and worried) by my decision to pursue sciences at ‘A’ and degree level. My practical, logical and inquisitive personality also made science the more obvious choice I think, and I really enjoyed it - I’m much more likely to give something 100% if I’m really interested in it. What inspires you about molecular bioscience? The most inspiration things as a cell biologist in academia are that you learn something new every day, can contribute to the greater understanding of how cells work and hopefully help understand how this impacts on disease processes. That’s why I started out in science and what drives me every day. I also love

collaborating with other researchers in different disciplines as it can allow you to test questions in your own research you previously thought were impossible or inaccessible. I can’t think of any other jobs where you get to do that… What’s been the greatest challenge in your career so far? The nature of running a research team in academia means it is rarely a 9–5 job. That was a particularly big challenge when I first started out as a new group leader. I figured out very quickly that being able to multi-task and prioritise was essential to keep on top of things and free up time to have a life outside the lab, otherwise you drown in it all. Of course I’m still learning, but I feel like I now have the best of both worlds in most respects. What do you do in your spare time? I’m very keen on running and like to try and get out whenever I can (which is not as often as I’d like these days!) – it’s particularly great when I’m away at conferences for escaping and re-setting my frazzled brain! Ambassadors are a key group of members that help us to raise awareness of the Biochemical Society, promote its activities, recruit new members and act as the Society’s point of contact at their institution. If you would like to get involved as an Ambassador, please contact: [email protected].

Evolving Molecular Bioscience Education 12–13 April 2018, Chester, UK Since before Roman times Chester has been an important city in the UK where people from many places and backgrounds come to discuss the world. In the Victorian period people escaped to Chester from the busy cities nearby to have space for thought and reflection. In April over 50 bioscientists from across Europe followed in their footsteps, escaping their campuses to meet in Chester to consider the latest challenges in molecular bioscience education. Following on from the success of two previous conferences, participants took part in a mixture of talks, posters and small group sessions covering current practice and developments in bioscience education. The workshop was themed around four areas: • Sharing best practice through research and across Europe • Teaching large cohorts • Undergraduate research projects • Teaching postgraduate and international students The conference opened with a presentation from Dee Scadden (University of Cambridge) who received the first ever Biochemical Society Teaching Excellence Award. She gave an interesting talk covering her online learning practice at Cambridge which has involved developing a variety of online learning resources accessed through the university VLE. Interesting developments from FEBS were then presented, in particular, with regards the FEBS online network and the new education section of FEBS Open Bio. How to publish educational research and editors ‘tips for success’ were presented here and discussed along with avenues to share practice across Europe using this FEBS network. This was followed by several presentations on the topic of teaching large groups of students, in particular the use of apps and ‘super groups’ to engage students alongside the use of video to deliver and support teaching. Interesting solutions to the challenge of giving personalized feedback

to large cohorts were also presented and discussed. The issues presented by ‘commuter students’ were considered and the different challenges that they face and how we might engage them better in a bioscience course. The difficulties of providing research projects were addressed in three of the talks, looking at how to provide meaningful project experiences both in a large group, in collaboration with the brewing industry, and through other community-based activities. Although the evolution of these project types is partially driven by large student cohorts, research also showed there is a demand from students for a diverse range of final-year projects. The final session considered how the teaching of postgraduate students is supported across Europe and how to best support international students. An example of the use of ethics teaching to aid integration of a cohort of multinational students ws given as a way of using pedagogy to support a diverse student group. Posters presented a wide range of approaches to delivering and supporting learning, from card games, through spreadsheets, to virtual labs. The posters also considered such issues as ‘does student location in the lecture hall related to attainment?’, with surprising results. The poster sessions provided valuable networking time which was also available at the conference dinner held beneath the city walls overlooking the winners’ enclosure at Chester Racecourse. Sitting overlooking a challenging course provided an interesting stimulus to discussing the education of the ‘winners’ of tomorrow, helping them over the final furlong. The conference provided an important forum to share best practice in life science education and it is hoped that the next conference will take place in 2 years’ time. Mark Roberts (Queen Mary University of London, UK) August 2018 © Biochemical Society 43

Obituary Andre Darbre (1921–2018) Andre Darbre was born on 28 May 1921 in Birmingham to Swiss parents with a family tree traceable back to 1601. He went to Waverley Grammar School where his love of swimming and playing the violin were kindled for life. After matriculation in 1936, he was appointed junior librarian at Birmingham Reference Library, but, like many of his generation, achievement of professional qualifications was interrupted by the war years. He volunteered to join the Royal Armoured Corps and served for 5 years, initially posted to North Africa into the battle of El Alamein and then moving up through Italy from Sicily to Bari. It was at a military party in Bari that he was made aware of the need for fluent French speakers to help translate for the French Resistance, and for this service he was mentioned in dispatches and awarded war medals. After discharge from the army in 1946, instead of returning to the reference library, he registered as a student at the University of Birmingham to read biochemistry. He graduated with first class honours in 1950. Little did he realise then that his daughter would graduate from the same university, from the same department, with the same degree and the same classification of degree 23 years later. And furthermore, that his granddaughter would also read biochemistry at university. Although he did not return to work at Birmingham Reference Library, he often popped in to see old friends. It was there that he met my mother, and they were married at Yardley Parish Church on 9 July 1949. My father started PhD studies, but grants were small in those days, and it was at that time that I was born, his only child, which focused the need for family stability. He applied for and was offered a university lectureship in biochemistry at King’s College, London, where he stayed all his working life. He was promoted to Senior Lecturer and then to Sub-Dean of the Medical Faculty, and always remained very proud to have been a part of King’s College. Most of all, he loved the students and encouraging them in their study of biochemistry. His love of supporting students led to his appointment in 1954 as National Assessor for HNC and HND in biochemistry and applied biology, and later as national examiner for the Institute of Biology, appointments which he held for 25 years.


Of course, academic life is an interwoven mix of research as well as teaching. He started his research with a PhD thesis entitled “The distribution of inositol in germinating cereals and pulses as determined by microbiological assay” which focused his research career into methodological development and turned him into one of the pioneers of gas chromatography. As a protein chemist, he gave much of his life to developing this emerging technology, which after later incorporating mass spectrometry, has become an essential component of analytical measurement. It is particularly fascinating to reflect on the miniaturization in biochemical research methodology over the past few decades, and in this context the contrast between the long fragile glass columns I watched my father make by hand to the small metal columns used today. He published many papers on gas chromatography and wrote several books, the last of which was translated into Russian and sold internationally. He retired in 1982 during one of the periods in university life when the universities needed to downsize. He reduced to 3 days a week before fully retiring a few years later, an excellent way of completing outstanding research and adapting to retirement life. Coincidentally, his granddaughter was born around that time, followed by his grandson a few years later, which redirected his focus for the future. He and my mother were devoted to their grandchildren. Every Wednesday and Thursday for over 20 years, they met their grandchildren from school and cooked a family supper. This family support for the next generation was the mainstay for my own scientific career. Andre Darbre died peacefully at the age of 96 on 21 March 2018 with his family around him, the last member of his generation in our family. We will miss him very deeply, but together with numerous ex-students, both undergraduate and postgraduate, in many corners of the globe, we will always remain grateful for all he gave to us, especially his enthusiasm for biochemistry which remained with him to the end

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Philippa Darbre-Gee (Professor Emeritus (Oncology), University of Reading)

Obituary Hubert Greenslade Britton (1925–2017) Professor Hubert Greenslade Britton, Emeritus Professor of Chemical Physiology at St Mary’s Hospital Medical School, Paddington and a lifelong member of The Biochemical Society died at the age of 92 in Salisbury on 3 October 2017. Determinedly dedicated to scientific research, he continued to do research and write papers until well after his retirement. His interests spanned from enzymology and membrane transport to placental and foetal physiology, metabolism and endocrinology. In enzymology, he is known for the induced transport method for analysing enzyme kinetics. Son of Edith and Professor Hubert T.S. Britton, Hubert went to Hele’s School, Exeter, before studying chemistry at University College Exeter, where his father was Professor of Chemistry. He completed his PhD on potentiometric titration. After studying medicine at Trinity College Cambridge and University College Hospital, he found a position in the physiology department at St Mary’s, Paddington. At St Mary’s, Hubert joined Professor Huggett’s group investigating foetal nutrition and placental function and, together with Pauline Alexander and D.A. Nixon, there followed more than 50 papers describing the metabolic roles of the placenta, including its production of fructose, and foetal endocrine function. His work on transport processes was pioneering, with the first published paper on the transport of radiolabelled glucose in the erythrocyte and the mathematical modelling of flux across the red cell membrane. In a series of single-author theoretical papers, Hubert applied the mathematical models used for studying flux across membranes to chemical reactions and enzymatic processes, an approach called the induced transport theory and method. With J.B. Clarke, Hubert demonstrated the practical utility of the method by showing that the interconversion of glucose 1-phosphate to glucose 6-phosphate by phosphoglucomutase must involve the intermediates of glucose 1,6-bisphosphate and a dephosphorylated form of the enzyme. Subsequent studies on phosphoglycerate mutase, hexokinase and pyruvate kinase led to him becoming a true mechanistic enzymologist. A productive collaboration with Professor Santiago Grisolia and colleagues over three decades began with a sabbatical in 1970–71 at the University of Kansas Medical Center. His papers (with Grisolia and José Carreras) on the mechanisms of diphosphoglyceratedependent and independent phosphoglyceromutases remain a mainstay on the knowledge of these enzymes. After Grisolia became Director of the Institute

for Cytological Research in Valencia, Hubert became a regular visitor to Spain working with one of us (V. Rubio) on carbamoyl phosphate synthetase (CPS1) which mechanistically at the time was a complete ‘black box’. Hubert applied his modelling talents to successfully predict the entry of radioactivity into the products formed from labelled substrates in all day (and often all night) pulse–chase experiments that were carried out in a (literally freezing) cold room. Innovative isotope scrambling experiments followed for proving enzyme-bound intermediate formation using NMR and ATP labelled with 18O at specific positions, in collaboration with Brian Sproat and Gordon Lowe at the Dyson Perrins laboratory in Oxford. Further CPS work focused on CPS1 activation by N-acetyl-L-glutamate (NAG), showing that it was exclusively an allosteric process. These pioneering studies, corroborated by the recent elucidation of the crystal structure of human CPS1, have played an important role in understanding the effects of mutations found in patients with hyperammonaemia due to CPS1 deficiency. Hubert remained loyal to St Mary’s Hospital Medical School throughout and was particularly proud to work where Alexander Fleming discovered lysozyme and penicillin. He dispatched several letters to The Times stoutly defending Fleming’s key role in those discoveries when this was under question. He taught physiology to many generations of medical students and supervised many BSc students. He was rewarded with a personal chair in chemical physiology by the London University in 1977. After retiring from St Mary’s in 1990, Hubert and his wife moved to Salisbury. He became a member of the local Civic Society and History Society and took up the cause of the Salisbury water meadows, which were under threat from a road development. Hubert had a mischievous, if somewhat unique, sense of humour. He enjoyed walking and used long walks to discuss anything scientific at length and in detail, from the formation of the universe to integrated circuits and the design of power-assisted braking in cars. When not immersed in the midst of piles of papers and journals (which gradually occupied all the space at home and work), he would play the piano, on which he was self-taught. He married Joan (Judy) Kelly in 1954, who died in 1999. His twin sister died 6 weeks before him. He is survived by his five children.

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Vicente Rubio and Thomas Britton


News Introducing the Industry Representative The Biochemical Society is committed to bringing together molecular bioscientists and supporting our members across the community. To this end there has been a renewed focus on those working in the industrial, biotechnology and academic drug discovery sectors. By way of background, the Society’s membership has historically been largely made up of academics, with a smaller number of members working in industry. In 2015 an Industry Strategy was developed by the Head of Membership Engagement with the aim of providing a platform for collaboration, facilitating innovation and supporting links between academia and industry.

Malcolm Weir (Industry Representative, Biochemical Society Council of Trustees; Heptares)

As part of the Society’s Industry Strategy, an objective was set to increase the number of industry representatives on committees and an Industry Representative was introduced as a Trustee role as part of the Governance Review which took place in 2016. I became the Industry Representative on the Council of Trustees in 2017 and I work with the wider team at the Society to broaden our involvement with industry and to address the needs of members working in industry. I am a biochemist by background (both my BSc and PhD are in the discipline) and I am still deeply involved in molecular bioscience research. From PhD, I entered the pharmaceutical industry (GlaxoSmithKline) and after 17 years in drug discovery I moved into the entrepreneurial world of biotechnology, as CEO of Inpharmatica (bio/chemoinformatics) and then co-founding the MRC spin-out Heptares, now upon acquisition a part of Sosei Group, where I continue as R&D Director. At Sosei Heptares, we have transitioned molecules invented by structure-based design into clinical development. Academic interactions continue to be crucial to our success. I still look back with fondness at the important role the Biochemical Society played in my early career, especially Harden conferences and other meetings. Seamless interaction with industry is critical to making the most of cutting-edge academic research, and I hope my experience can support the work of the Society’s Industry Strategy and ensure that industry interests and skills are represented at every level of the Society, including at Trustee level. At June 2018, 10.7% of the Society’s governance structure is occupied by members from ‘Industry’. Work around the Society’s Industry Strategy is also supported by the Industry Advisory Panel, a small and informal network of members and non-members who provide ideas and feedback on various industry facing initiatives.


The overarching objectives of the Biochemical Society’s Industry Strategy are to increase: 1. the representation of industry within the structure and governance of the Biochemical Society including Council, Boards, Committees and Panels 2. t he number of members from an industry background In turn, it was felt that that this would ensure that the needs and interests of those working in biochemical and related industries were met, in line with the overall Biochemical Society’s objective of advancing the molecular and cellular biosciences, both as an academic discipline and to promote its impact on areas of science including biotechnology, agriculture and medicine. Over the last 20 years, biochemistry has evolved to become an integral part of industrial research and development, in particular in the pharmaceutical and biotechnology sectors, but also reaching well beyond biomedical sciences into other areas of business. Traditional barriers between industry and academia have happily been eroded and translation from basic science to societal and economic impact greatly improved. Discussions at the Society’s Strategy Retreat in November 2017 determined that industry will remain a key area of strategic focus for the Society as it moves to closer alignment with and expands its activities to serve the wider community. Initially within this theme, molecular bioscientists working in industry will be a priority group and this focus on industry will form a cornerstone of the Society’s next Strategic Plan for 2019–2021. At present, the Society’s various committees are considering how they can support the

News expansion and strengthening of networks so that the Society can move beyond being a primarily academic community and expand to serve those with both professional interests in the molecular biosciences. From 2019–2021 this is likely to include the development of membership offerings for apprentices and technicians and expanding our careers support and information, promoting the opportunities offered by biochemistry and molecular biology through academic and vocational pathways. Other options being explored include providing professional development for technicians (for example, through the Society’s online training portal), introducing professional registration, continuing to support teachers at all levels, to

develop their skills and knowledge and to facilitate encounters with industry and academia for teachers and students, and continuing to use the Industry and Academic Collaboration Award to increase dialogue with those working in a commercial setting and to grow awareness of the Society and its relevance to those working in non-academic settings. You can read about some of the ways we are currently supporting industry on our website at: www. biochemistry.org/Membership/SupportingIndustry. If you have ideas about industry-facing initiatives or opportunities that you think the Society could be exploring, please email Laura Woodland, Head of Membership Engagement ([email protected]).

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Acylation of intracellular and secreted proteins: mechanisms and functional outcomes 10–12 September 2018 Old Ship Hotel, Brighton, UK More information at bit.ly/Protein_acylation


News Royal Society of Biology News

Strengthening the bridges between the public and policymakers Bringing together the sciences, as well as presenting and discussing collective views with policymakers has been a big feature of the recent, typically busy months, at RSB. Indeed, the summer calendar has been geared around events big and small to achieve this. In June, we hosted Parliamentary Links Day, which brought together members of the biosciences and STEM communities, Mark Downs policymakers, politicians, and other sector CSci FRSB leaders to discuss the current climate for (Chief Executive, Royal science and how to build the best future. Society of Biology) The event, opened by the Speaker, included keynote addresses from Norman Lamb MP, Chair of the Commons S&T Select Committee and Chi Onwurah MP, Shadow Minister for Industrial Strategy Science and Innovation, with panel discussions hosting sector leaders to discuss the strategy and its delivery. In addition, Rebecca Endean, Director of Strategy and the newly formed UKRI, and Dr Patrick Vallance, newly-appointed Government Chief Scientific Adviser had an opportunity to give their first addresses during the event. Links Day is an important opportunity for the science community to engage with policymakers and sector leaders. The session featured two dynamic panels discussing the strategy, its outcomes and its delivery, with the audience too being a very active participant in the discussions. Overall the day allowed the sharing of ideas and views with the policy experts – a satisfying aim to achieve. The development of the Industrial Strategy of course continues beyond Links Day, and I was pleased to see recognition of our evidence and recommendations in the report published by the House of Lords’ Science and Technology Committee following their inquiry into the Strategy. We highlighted that there was a real potential for missed opportunities if an insufficiently broad definition of life science was used throughout, and the first recommendation of the Lords report is that Government should identify areas for sector deals across the life sciences in addition to health and biomedical areas. We will continue to emphasize the importance of recognizing the breadth of the lifesciences, which should always include biotechnology, agriculture, plant science, animal science and climate change mitigation and adaptation, among others, and provide opportunities for collaboration across specialisms.


In smaller and specialist meetings we have been taking the opportunity to put across the bioscience views and priorities, for example with Lord Henley, Parliamentary Under Secretary of State at BEIS, and with groups such as the Heads of University Biomedical Sciences. Being able to draw upon the examples and data from our member community continues to be a huge asset in flying the flag for bioscience and the support, policy, training environment, and regulation we need. As well as reaching the policy professionals and Government policymakers, we’ve also been busy delivering outreach and engagement projects to a variety of audiences. We aim to help empower members and volunteers to share and discuss different bioscience topics with different audiences, through activities we run and events we attend, alongside the programme of school competitions we offer. The RSB special interest group, UK Biology Competitions, held the Education Awards ceremony in July, to celebrate some of the 62,000 pupils who took part in our three school competitions this year alongside outstanding biology teachers and schools. The ceremony exemplifies not only the popularity of our school competitions, but how they are valued by schools, by us, and by those who will hopefully be the next generation of bioscientists. Our outreach and engagement work with The Biology Big Top, a collaboration of engagement teams across Member Organisations including the Biochemical Society, has been busy attending events, festivals, exhibitions and more, stimulating conversation and building enthusiasm for the biosciences. This year we hope that Biology Week will exceed last year’s total of 100 events taking place worldwide, crowding in the enthusiasm of the community. On a broader note, we will be holding our first ever outreach and engagement symposium in the autumn, in partnership with the Biochemical Society and others, bringing together the professional and volunteer biosciences outreach community to learn, share best practice, and build ideas. Links Day and Biology Week may look far apart, but they are both very much about the totality of bringing the biosciences community closer together, bringing scientists and policymakers closer together, and also reaching out to new audiences too. Together we can have enhanced impact on those issues that unite us all and affect us all equally. The Biochemical Society and its members are essential partners in this and I look forward to our next set of work together.

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News CEO Viewpoint

Kate Baillie (Chief Executive, Biochemical Society and Managing Director, Portland Press)

At the time of writing, the Society had just announced the election for the next Chair of the Biochemical Society, who will step into position from July 2019, when Professor Anne Dell steps down. It has been encouraging to observe a really impressive turnout so far; within just 24 hours of being invited to cast votes, 10% of members had done so. In June, we announced the winners of our popular Science Communication Competition. The creativity of our student members never fails to impress the judges, with entries this year spanning diverse topics from cancer to kuru – and as usual the competition proved very popular, with over 40 entries. In particular, I would like to congratulate our winners: Victoria Bolton for her prize winning article, “Toxo and Jerry – about cats, mice and behaviourchanging parasites”, and Jirayu Tanprasertsuk for his video, “Eating for your eyes”, which won first prize in our video category. More information about these entries is featured on page 32. Portland Press has recently secured a new subscription deal for 2018 and 2019 with the CAPES consortium in Brazil, which is worth $154,000 per year and it is worth noting that success in achieving this important sale was helped significantly by our status as a Society publisher. Synergies across the Group have helped towards this success and in particular the popularity of the Portuguese translation of the Society’s Sciberbrain resource – which aims to equip teachers for classroom discussions of controversial aspects of science – was influential in securing this deal. Profits made from our publishing activities via Portland Press are donated directly to the Biochemical Society to spend on its charitable activities, and links such as these continue to be invaluable in ensuring the success of our publishing business and, in turn, a strong future for the Society and the services it provides to the molecular biosciences community.

The Society continues to be very active in the policy arena, and has recently fed into the Health and Social Care Committee’s inquiry into antimicrobial resistance, which will help to shape the government’s priorities for its next AMR strategy due to be published later this year. We have also commented recently on the House of Lords Science and Technology Committee’s report, ‘Life Sciences and Industrial Strategy: Who’s driving the bus’. You can read our Honorary Policy Officer, David Pye’s statement on the strategy here: bit.ly/2I2fg9u. Our public engagement team have been busy this summer, touring with our new interactive Scientific Scissors activity, which explores new genome editing technologies, at science festivals up and down the country – such as the forthcoming Ipswich Maritime Festival (18–19 August). All of our hands-on public engagement activities are designed to be easy and affordable for members to run themselves; if you’d like to try Scientific Scissors for yourself, you can download all the materials from our website (bit.ly/2JFV8zZ) free of charge. Next month, the Society’s scientific events programme includes the Biennial International LRRK2 meeting (2–4 September) in Padua, Italy. Closer to home, our 84th Harden Conference on single-molecule bacteriology takes place at Lady Margaret Hall in Oxford (9–12 September) and the team will be in Brighton for ‘Acylation of intracellular and secreted proteins: mechanisms and functional outcomes’ (10–12 September). To find out more about the Society’s scientific events, go to bit.ly/1fJe9OL. There is still time to apply for one of the Society’s scientific outreach grants. Both members and nonmembers can apply for grants of up to £1,000 to assist with the costs of running outreach events that communicate the excitement of molecular bioscience to young people and the community. The current round of applications closes on 24 September 2018 – visit bit.ly/1Bkrh2d to browse our previous outreach activities and to apply.

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Book Review I, Mammal: The story of what makes us mammals by Liam Drew If you want to know exactly what differentiates us, the placental mammals, from all the other members of the Animal kingdom, both past and present, read this book. Liam Drew, a neurobiologist by training and now a successful science writer, has produced a very readable account of the evolutionary history of mammals, starting over 200 million years ago. It covers in some detail all the physical characteristics, which are unique to mammals, many of which might be obvious to the casual observer, but some are more surprising, such as the arrangement of the bones of the middle ear, or that mammals alone have a lower jaw which is a single bone. Everybody knows that only mammals lactate and that new-borns live entirely on their mother’s milk for a period, which may vary from a few days to many months. The author, however, takes us on a journey, describing the development of mammary glands from the earliest modified sweat glands which produced a fluid which may have had antimicrobial qualities and may also have

The work has just begun By Benoît Leblanc

(http://peopleinwhitecoats.blogspot.co.uk)


prevented drying out of recently fertilized eggs in protomammals, but certainly had no nutritional qualities, to the ability of seal pups to double their birth weight in a few days, entirely dependent on their mothers’ hugely beneficial milk. We also learn that mammals are provided with a hard palate separating the nasal passages from the mouth, which allows the infant to breathe and suckle at the same time. When preparing this book, the author listed those features, which he felt, were typical of mammals, and these form the chapter headings. They include scrotums, X and Y chromosomes, reproductive organs, placentas, mammary glands, skeletons, warmbloodedness, the senses, and large brains. Interspersed with the details of development through geological time are numerous personal anecdotes about the birth and development of his own daughters and his reaction to these events. This turns what might otherwise be sometimes dry descriptions of the differences between monotremes, marsupials and placental mammals into a most entertaining series of stories ranging from our common ancestor to the trials and tribulations of premature birth and special care units. The book is thoughtful, comprehensive and sometimes a little surprising. It is highly recommended to anyone interested in our place in the natural world. John Albert (Cambridge, UK)

ADVERT SPACE A BIOCHEMICAL SOCIETY SCIENTIFIC MEETING

The Changing Landscape of Research on Ageing: Models, Mechanisms and Therapies 7 November 2018 Glasgow, UK

Find out more at bit.ly/research-on-ageing

THIS SCIENTIFIC MEETING IS ALSO AVAILABLE AS A LIVE WEBINAR

Back reactions

Prize Crossword N.A. Davies

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5. Relating to a small life form, typically bacterial (9) 9. Cultivated produce (4) 10. Food gelling agent often refined from seaweed (8) 11. The power of endurance in the face of adversity (9) 12. Food source supplying essential amino acids (7) 13. Science of land, soil and crops (8) 16. Three part arthropod (6) 19. That which promotes a vigorous immune response to something that is harmless to most (8) 20. Single-cell fermenting factories (5) 21. Deficiency leads to sideropaenia (4)

1. When 16 across is your food of choice (11) 2. Ability to withstand (10) 3. Possibly golden to increase dietary 15 down (4) 4. Fruit _____21, created to prevent deficiencies (6) 6. Nourishing substances (9) 7. Tactile sensation of a product (7) 8. Abnormal plant condition interfering with vital processes (7) 14. Having not undergone processing procedures (7) 15. Retinol (7,1) 17. Essentially a white tasteless carbohydrate (6) 18. Bean primarily grown for its protein content (3)

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Solutions to the crossword featured in the June 2018 issue are: Across: 2. Male, 3. Pregnancy, 6. Oocyte, 8. Cervix, 11. Conception, 12. Gametes, 14. Conjugation, 16. Zygote, 19. Uterus Down: 1. Female, 3. Procreation, 4. Cycle, 5. Fecundity, 7. Contraception, 9. Intercourse, 10. Sperm, 13. Ovum, 15. Testes, 17. Birth,18. Ovary

Crossword Competition

Win This month’s crossword prize is a Science4you Sweet Factory Kit. Simply email the missing word, made up from letters in the highlighted boxes to [email protected], by Monday 3 September. Please include the words ‘August crossword competition’ in the email subject line.

Congratulations to the winner of the June competition: Craig Hughes The missing word from last issue’s competition was OFFSPRING. Craig Hughes received a Science Museum Set of 4 Chemical Compound Coasters. Terms and conditions: only one entry per person, entrant must be a current Biochemical Society member; closing date Monday 3 September 2018. The winner will be drawn independently at random from the correct entries received. The winner will receive a Science4you Sweet Factory Kit. No cash alternative available. No employee, agent, affiliate, officer or director of Portland Press Limited or the Biochemical Society is eligible to enter. The winner will be notified by email within 7 days of the draw. The name of the winner will be announced in the next issue of The Biochemist. The promoter accepts no responsibility for lost or delayed entries. Promoter: Biochemical Society, Charles Darwin House, 12 Roger Street, London WC1N 2JU; do not send entries to this address.


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Drawing a protein standard curve Extracting data from objects Drawing an enzyme kinetics plot Customizing and reusing plots Getting your data into R for exploration

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Biochemistry: the Molecules of Life Starts 1 October 2018 Targeted at students aged 15–19, this three week MOOC (Massive Open Online Course) will provide an introduction to biochemistry, ideal for those thinking of pursuing studies in molecular bioscience.

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