by Heidi Norman
This may not prove easy, with pharmaceutical companies reluctant to invest in drugs that require only short courses – unlike profitable medications such as cholesterol-lowering statins, which people end up using all their lives. ‘Major pharma has withdrawn to a large extent from the antibiotic discovery process,’ Rood says.
Global charities like the Wellcome Trust and the Bill and Melinda Gates Foundation have stepped into the breach. And Hill-Cawthorne says that as an anti-TB drug, teixobactin could qualify for one of the FDA’s accelerated approval programs.
This happened recently with bedaquiline, another TB drug. ‘But it would still be a few years before it becomes available.’
And while successful negotiation of these regulatory hurdles would give the world a new drug against TB and MRSA – not to mention scarlet fever, perhaps the most feared of the old illnesses threatening a comeback – it won’t work against the ‘Gram-negative’ bacteria responsible for diseases such as dysentery, typhoid, severe gastroenteritis and many surgical infections.
Gram-negative bacteria, so called because of the way they react to the ‘Gram stain’ dye test used to identify microbes, are structurally different from Gram-positive bugs like staphylococcus, bacillus and listeria. Gram-negative bacteria have thinner walls with two rather than one set of membranes. Antibiotics that attack them are often ineffective against Gram-positive bacteria, and vice versa.
And while Gram-positive bacteria would initially be defenceless against this new class of antibiotics, resistance would only be a matter of time. Boulos says bacteria reproduce asexually, with some species spawning new generations in as little as a few minutes.
Bacteria have ‘highly sophisticated’ means of exchanging genetic material, he says, and mutations are frequent. ‘The genetic material passed from one generation to another is constantly changing, exacerbated by selective pressures in their environment (such as) antibiotics and other hostile (microbes). Bacteria have the upper hand in this race.’
Eman Aleksic, a TB specialist with the Burnet Institute in Melbourne, says the size of bacteria cells is part of the problem. ‘Their DNA’s bigger (than viruses), so there’s more chance across the lifespan to evolve and change. It’s just so big, it spontaneously mutates.’
But the size of the cells means they harbour more potential drug targets than viruses, and advances in genomics are helping to find them. Aleksic co-authored a recent study which identified 15 such genes in drug-resistant ‘Beijing’ strains of TB.
But the same study, published in the journal Nature Genetics, underlines just how resilient these strains are – with the advent of antibiotics proving just a blip in their evolution. A declining population coinciding with rising antibiotic use in the 1960s was reversed in the early ’90s, when the Soviet Union’s public health system collapsed.
Aleksic says such events squeeze the availability of antibiotics, allowing resistance to develop when people fail to take full courses. The same thing still happens in countries such as TB-ravaged Kiribati, where authorities personally monitor sufferers taking their drugs under a scheme called ‘directly observed short course therapy’.
‘There aren’t that many drugs available for TB, (so) we can’t jeopardise those antibiotics for the rest of the population,’ Aleksic says. ‘We want to make sure people take their drugs on time, daily, the way they’re supposed to for the duration of their treatment.’
She says many such interventions are needed to combat antibiotic resistance. And Hill-Cawthorne says antibiotic governance is the key.
‘It’s part of a repertoire of things we need to put together on a global scale to stop resistance. We need to make sure you only use even these new drugs when they’re completely appropriate – (that) they’re not used by all doctors for all conditions, and they’re not used in agriculture. (If) they appear in food products at low concentrations, it increases resistance.’
Hill-Cawthorne concedes that the use of antibiotics is hard to control in countries like India, where they are readily available over the counter. But the professional oversight of antibiotics in places like Australia is grounds for hope, he says.
‘There is a growing recognition, particularly in countries like the UK and US, that this isn’t just a health care issue. It’s something that medicine, vets and agricultural specialists all have to work together to solve.’
Why aren’t we dead yet?
Beating the odds
Lost in a floral desert
Manu Saunders
Mass-blooming crops create a glorious vista, and it’s easy to assume that bees and other pollinators love it as much as we do. It’s true that peak bloom in crops attracts many pollinators – how could they resist? – but the flowers last only a few weeks, after which the field becomes a floral wasteland. This short-lived surplus of blossom can betray pollinators that build nests deep inside the field. If no resources are available within flying distance when the next generation emerges, they will not survive.
The attraction of these crops can also be detrimental for native plants nearby that miss out on pollination because their neighbours are getting all the attention. This has been called the Circe Principle, after the seductress in Homer’s epic poem who waylaid Odysseus on her island, keeping him from his true course.
Because mass-flowering monocultures, like canola fields and almond plantations, are a fairly recent addition to Australia’s agricultural regions, there is still much to learn about their long-term ecological consequences.
Wild pollinators
European honey bees are the favourite crop pollinators because they are easily managed. Yet, around Australia, thousands of wild insect species pollinate crops for ‘free’. The challenge for conservation is that these wild pollinators can only be managed indirectly, by ensuring suitable habitat and resources are available to sustain long-term populations.
Australia has nearly 2000 native bee species, some of which, like the stingless sugarbag bees, can be managed as working pollinators. There are also more than 400 butterflies and a few thousand wasp, fly, moth, beetle and ant species. Not all are dedicated pollinators. Flowers may be a minor source of food in their adult diet if they mainly prey on or parasitise other insects. Sadly, pollinating insects commonly regarded as pests, like blowflies or sawflies, are rarely acknowledged to have a positive side.
Non-bee pollinators are often overlooked in agriculture, where efficiency trumps effectiveness. Although some flies, sawflies and others carry a lot of pollen grains, sometimes more than bees, they are considered less efficient pollinators because they visit flowers less frequently, so their pollination services can’t be guaranteed.
Yet these ‘hobbyists’ can be just as important for pollination as the very efficient ‘career’ bee pollinators. Many studies have found that crop yields are higher when multiple insect species visit flowers. This is more than simple maths. Different insects may pollinate different parts of a plant – in Californian almond plantations, honey bees showed a preference for the top section of trees while wild pollinators visited the lower parts. And in some crops, honey bees are more likely to switch between male and female flowers (and achieve fertilisation) after encountering another type of insect on a flower than if they encounter another honey bee. This type of competition between species is common in natural ecosystems, and greatly increases the chances of cross-pollination for plants. In monoculture crops where wild pollinators are few and far between, honey bees can usually forage on a single flower for as long as they like.
Pollinator communities have co-evolved with flowering plants, so floral and pollinator diversity go together. Wild pollinators, particularly native bees, need habitats with diverse plants and structures. Flowers vary greatly in the quantity and quality of pollen and nectar on offer. Some flower visitors eat pollen grains, others the nectar, and some both. They also vary in their colour, scent and shape preferences. Beetles tend to favour pale flowers with strong, fruity scents, while native bees often go for brig
ht yellow or purple flowers with high ultraviolet contrast against vegetation. Large flies are most often found on flat or bowl-shaped flowers, which give their short mouthpieces easy access to nectar. These are generalisations, and flower choices vary among families, species or individuals, depending on environmental factors and whether pollen or nectar is the food du jour.
Insect pollinators also need other plant resources, like saps and resins. Stingless bees use plant resins as chemical defence against predators and pathogens, and a recent study by Nora Drescher and others in south-east Queensland showed that a mixture of resins can be more effective than just one. Pollinators also need to nest or overwinter somewhere, such as under bark, leaf litter, in plant stems, stone cavities or dead wood. And if there is no food around when the young insect emerges from its nest, the nest-building will have been in vain. This is where mass-flowering crop landscapes fall short.
Almond blossom monocultures
Fruit tree blossoms have inspired poets, artists and romantics for centuries, and symbolise life, fertility and awakening in many ancient and modern cultures. There is something inherently joyous about a whole tree, still leafless, bursting into bloom at the first hint of warmth, as if it can’t wait any longer for winter to be over. As one of the first fruit trees to awaken from hibernation, almond trees have a strong emotional effect. Their ‘superb and fearless flowers’ aroused DH Lawrence to poetic rhapsody:
The alien trees in alien lands; and yet
The heart of blossom,
The unquenchable heart of blossom!
I spent two glorious springs in blossoming almond orchards investigating wild pollinator communities and habitat characteristics. In late August, the eerie winter stillness of a leafless plantation is shattered into a million pieces of light by a coordinated budburst, making it impossible not to get excited about spring when it arrives.
The semi-arid mallee regions across southern Australia, with dry summers and wet winters, provide ideal conditions for almond trees, which originate from the desert regions of Iran and the Middle East. Almost two-thirds of those grown commercially in Australia are in north-west Victoria, where I did my research. As the industry expands, huge plantations, many exceeding a thousand hectares, are encroaching on mallee woodlands and shrublands. Ecological research in the region has mostly focused on fire and wildlife dynamics. Little is known about how the expansion of plantations may affect the unique mallee ecosystems.
Almonds are managed as intensive monocultures. Grass and weeds are sprayed and mown to reduce byproduct in the nut piles and to allow the mechanical sweepers and shakers that harvest nuts at the end of summer to travel unimpeded. From late August into September, the landscape sparkles with almond blossoms. They are almost completely dependent on insect pollination for fruit set, and for this service commercial producers rent European honey bees. Every year, more than 100 000 hives are trucked into Victoria’s almond plantations for the few weeks of bloom, costing growers millions of dollars.
Using coloured pan traps, I collected insects in almond plantations and native mallee vegetation, and found very few native bees, hoverflies and other pollinating wasps and flies inside plantations. They are not averse to almond blossom, but usually visit flowers only at the edges next to native habitats. The deeper you go into plantations, the less plant diversity there is and the fewer native pollinators.
Native insect pollinators are far more plentiful in small organic orchards, where grasses and weeds provide diverse food sources. Most wild pollinators have a home range of less than one kilometre, so are more likely to reach the centre of small than large orchards. Many, particularly bees, prefer open vegetation, like grassland, open woodland and heath. Native bees can be found in the centres of huge open fields of crops like canola, but tree crops are too much like a dark forest to be inviting. Conserving wild pollinator diversity in farmland therefore requires crop diversity and a mix of natural and agricultural systems.
Beauty is in the eye of the beholder. A plantation with measured rows and clean floors is a scene of orderly beauty, but pollinators don’t care for tidiness. They prefer all the niches and resources of disorderly shrublands and woodlands, with flowering herbs randomly interspersed among messy leaf litter and dead branches.
The vanishing writers
Love bug
Field guide to the future
Revisiting Milgram’s shocking obedience experiments
Nick Haslam and Gina Perry
Chances are you’ve heard of Stanley Milgram’s obedience experiments. In 1961, Milgram recruited pairs of volunteers to take part in a ‘memory test’. One volunteer was given the job of teacher, the other, learner.
Each time the learner gave a wrong answer on a memory test the teacher was instructed to give the learner an electric shock and to increase the voltage with every error. What the teacher didn’t learn until later was that the learner and experimenter were actors and the machine was a prop.
In his first publication about the research, Milgram reported that a clear majority of participants inflicted what they were led to believe were painful, if not lethal, electric shocks to the learner. Most of us, he concluded, can be induced to torture someone else at the behest of an authority figure.
Milgram’s work appeared to say something profound about human nature. But there is no general agreement among psychologists about the meaning or implications of the research.
Did it, as Milgram argued, illuminate the Holocaust, whose executioners claimed they were merely following orders? Did it reveal the capacity for evil lurking in our hearts? Or did it simply demonstrate Milgram’s own blind-spots?
We decided to take a closer look at the statistical claims of Milgram’s research by revisiting his papers and data related to the obedience experiments in the archives at Yale University.
Milgram’s headline-grabbing conclusion that 62.5 per cent of people obeyed instructions appeared to show most of us can be led to kill at an authority’s bidding. But this statistic came from his second, and most widely reported experiment, which involved just 40 people.
In fact, Milgram conducted 23 different kinds of experiments, each with a different scenario, script and actors. This patchwork of experimental conditions, each conducted with a sample of only 20 or 40 participants, yielded rates of obedience that varied from zero per cent to 92.5 per cent, with an average of 43 per cent. Contrary to received opinion, a majority of Milgram’s participants disobeyed.
In some conditions, the experimenter told the teacher to stop instead of continue. Others had two experimenters give conflicting orders. There were conditions with female teachers, or groups of teachers (using confederates again) who pressured the participant to obey or disobey.
In some conditions, the learner drew attention to a heart condition, in another he made no verbal responses at all, and in another he only agreed to take part if he could pull out when he wanted.
In several conditions the experimenter was physically distant from the teacher. In others the teacher was seated next to the learner in the same room. In one little-known condition, the learner was a friend or relative of the teacher.
Finally, Milgram varied the setting in which the experiment took place. One condition took place in the industrial town of Bridgeport, far from the ivied halls of Yale, the study’s home base.
Making systematic sense of those variations did not interest Milgram himself, but we have published a first attempt in the journal PLOS ONE. Using his original data and backed up by research at Yale University’s archives, we synthesised data from 21 of his experimental conditions, involving 740 participants in all.
We classified the 21 conditions in terms of differing roles of the experimenter, teacher, learner and the relationships between the three.
Setting aside the broader problems with the experiment’s internal validity, evidence of participant scepticism, and the lack of standardised procedures, we aimed to tease out which of the many features of his different variatio
ns accounted for whether or not teachers went to the maximum voltage on the shock machine.
According to our analysis, the most powerful factor was whether or not the experimenter directed the teacher to administer the constantly rising shock levels. In conditions where the teacher was free to choose the shock levels, very few proceeded to the maximum voltage.
Obedience levels were significantly lower when there was dissent between the experimenters, when there was support for disobedience among the teachers and when the experimenter was absent from the room.
Interestingly, it was no higher when the experimenter was a more legitimate authority figure, or when the experiment was conducted in a more prestigious institutional setting.
By implication, obedience is strongest when authority figures give concrete directives, present a united front and maintain close contact with their subordinates. It is also strongest when subordinates lack collective support for resistance.
We found that the relationship between the learner and the teacher was equally important. Teachers were more likely to refuse to continue when the learner was physically close, when the learner was an intimate of the teacher and when the teacher had a direct link to the learner.
Obedience – in the Milgram paradigm at least – is not only a matter of the subordinate’s relationship to the authority figure. This is where most Milgram scholarship focuses, but it is only part of the story. Social relationships with people other than an authority figure are a powerful influence.
Ironically, because they were isolated in an experimental laboratory, Milgram’s subjects lacked the advantage available to others in the world outside when they are being coerced and pressured to obey. In the face of bullying, the best strategy is to find allies, form alliances, and stick together.
