The Best Australian Science Writing 2015 (25 page)

To further ensure that compromised, virus-manufacturing cells are not allowed to live, specialised
natural killer
(NK) cells seek out distressed body cells and destroy them.

Advanced infiltration tactics

After all this has been going on for a few hours, it is a pretty sure bet that a normal, healthy immune system dealing with a reasonable infection has managed to bring the situation under control. As I mentioned, the large majority of microbes that usually enter a body find themselves there by accident, and an important part of the immune system's job is to dispose of these accidental tourists quickly, before they start multiplying and making trouble.

Some invaders, however, are far less benign. Infiltrating the human body is what these pathogens do for a living, and they come prepared with the right tools and skills for the job. For instance:
Mycobacterium tuberculosis
bacteria get eaten up by the macrophage cells stationed in the lungs, but they trick the macrophages, so that once one swallows a bacterium, the germ can manipulate the macrophage in such a way as to prevent it from moving the germ into its
lysosome. M. tuberculosis
definitely does not want to enter the lysosome, because ‘lysosome' is an innocuous name for something a bacterium would call ‘the floating acid-filled chamber of explosive death'. This inner compartment of the macrophage is where it digests its prey; in effect, it's the macrophage's stomach.

Instead of fusing with the lethal lysosome, the bacterium stays inside a separate compartment within the macrophage, and feeds and multiplies inside it, turning the hunter into quarry. When the bacteria have multiplied so much that they've exhausted that
particular cell's possibilities, they burst it and leave. It's very hard for the body to stop them doing that, which is why tuberculosis is such a troublesome disease.

Other pathogens have similarly cunning techniques. In fact, for virtually any measure the immune system employs to protect the body, some pathogen or other has found a way to hide from it (or, as in the case of tuberculosis, inside it), circumvent it, stop it, use it for its own nefarious purposes, or destroy it. Just about any communication signal used by the immune system can be intercepted, exacerbated, or otherwise messed with: a type of strep bacteria can collect cellular proteins from its surroundings, thus concealing its true bacterial identity from recognition; malarial parasites hide inside red blood cells; HIV viruses target the immune system itself, attacking T cells and wreaking havoc on the immune response. It's a little like a burglar who specialises in burglarising police stations.
Chlamydia trachomatis
enters a cell and then prevents it from signalling it's been infected.
Neisseria gonorrhoeae
secretes a protein molecule that promotes cellular immunosuppression – in effect sending out a falsely reassuring signal that prevents the immune system from springing into action.

Every nasty pathogen has its own devious tactic for manipulating the immune system – otherwise it wouldn't be a nasty pathogen. It'd be an easily controlled, pushover pathogen, cleared up by the immune system with little to no fuss, and we wouldn't even know of diseases like tuberculosis, malaria, AIDS, chlamydia, or gonorrhoea.

Sniffing out the dodgy stuff

When I was at uni, I took a course called ‘Breakthroughs in Microbiology'. There were about a dozen students, and each of us was randomly assigned a different seminal microbiology paper, on which we had to present a short talk. Nearly all of the
papers were decades old, which to me, back then, meant that they weren't very interesting, and so I rejoiced to see that the paper I'd been allocated was only a few years old. Virtually hot off the press! And published in the esteemed journal
Nature
, no less. The subject was
Toll-like receptors
(TLRs), which are molecules found on cells of the immune system. The paper showed that one type of TLR, named TLR2, was responsible for identifying a type of molecule that almost all bacteria have on their outer coat, but non-bacterial cells never do. It's known as bacterial
lipopolysaccharide
(LPS). So when TLR2 senses the presence of LPS, it's a safe bet that bacteria are afoot, and an immune response is necessary.

So far, so good. I read the paper, summarised the findings, and went forth to find a few more recent papers on the subject so that I could provide background and context for my talk, like a good little student. But there I ran into trouble: something was amiss, and I couldn't tell exactly what. The papers I was reading seemed to be saying weird things that wouldn't settle neatly into my talk. Several frustrating weeks later, I figured out the cause of my confusion: the other papers were weird because they were
directly contradicting
my assigned
Nature
paper. TLR2 doesn't detect LPS at all; that was an error. A different Toll-like receptor, TLR4, is the one that really detects LPS. I know it doesn't sound like much when I put it like that, but this little fact was worth the 2011 Nobel Prize in Medicine.

The
Nature
experimenters weren't careful enough. The LPS solution they used wasn't sufficiently purified and was contaminated with a tiny amount of other bacterial elements, and these contaminants were the ones that provoked the TLR2 reaction. Our course lecturer, that crafty old devil, deliberately gave out an erroneous paper to demonstrate the fallibility of scientific papers (I never worked up the nerve to tell him just how awesome I thought that was).

This paper wasn't some sensationalist survey creatively misreported in the science news of a local newspaper. This was serious, respectable research published in
Nature
, and it was wrong. It took me a while to rid myself of the shudders conjured by the what-if scenario: what if I hadn't caught on to what was going on? I'd have delivered the talk as if the paper were correct, making a right proper fool of myself, and would most likely have had my arse handed to me on a plate. Research, even research published in prestigious journals, can and does produce errors. It's something that every scientist ultimately learns one way or another, and this was a good way of learning it: in a classroom rather than in the real world of research.

This little story, besides teaching what may be the most valuable lesson about science that I can think of, is both an introduction to Toll-like receptors, and something of a metaphor for the role of these same receptors and others like them: the innate immune system needs to be constantly vigilant, to be able to tell when something's not right, to sniff out the dodgy stuff and pass on the information. Or else we get our arse handed to us on a plate.

Will a statin a day really keep the doctor away?

Honest placebos

Robots on a roll

James Mitchell Crow

In a corner of the Port of Brisbane, close to the CBD, no human is allowed to tread. There are high fences, and a web of laser beams scans the perimeter. This land is inhabited by giant robots. Ten metres tall and weighing in at 65 tonnes, they thunder along at 10 metres per second on wheels almost the height of a man.

Welcome to the home of the AutoStrads: a 27-strong family of autonomous dockside straddle trucks that has lived and worked at the Patrick's Brisbane container terminal since early 2005. These eight-wheeled giants use radar, high precision GPS and a host of other sensors to pilot themselves around the site, working 24-7 to ferry shipping containers between quayside and roadside. In contrast to your typical human baggage handler, they are gentle with the cargo, placing each container with better than two-centimetre accuracy.

AutoStrads are the babies of Hugh Durrant-Whyte, who led much of their development at the Australian Centre for Field Robotics (ACFR) based at the University of Sydney. In late 2010, Durrant-Whyte left to become head of NICTA, Australia's centre of excellence for information and communications technology research.

The English engineer is somewhat of a paradox. Despite
heading a communications institute he has never owned a mobile phone. But then, he has never held a driver's licence either, and that didn't stop him teaching robots how to drive.

His work now largely concerns what takes place behind a screen, but he clearly enjoys casting his mind back to Australia's big outdoors and field robots. As we talk about his AutoStrads, I can't help thinking he must miss them, just a little.

In the late 1980s, Durrant-Whyte was one of the first robotics researchers to re-set their sights away from the endearing robots Isaac Asimov imagined in his
I, Robot
series, to no-nonsense, hard-working, un-cuddly ‘field robots'. His first prototype was an autonomous dockside vehicle, built in the early 1990s while he was still at the University of Oxford. ‘At that point it was by far the largest robot ever built,' he says.

Two decades later, humanoid robots – the research area Durrant-Whyte left behind – are still stuck in research labs. ‘To be honest, I'm not sure that field has progressed much since, simply because it is so hard,' he says. ‘If you think about where robots are having an impact, none of them are humanoid.'

But many of them are field robots: commercially successful autonomous machines such as the AutoStrad. And the country that has led much of this progress? Australia.

* * * * *

There's nothing small about the Pilbara in Western Australia. It is renowned for its vast, ancient landscapes, its parched red soil dotted with dusty-green gum trees, its oasis-like waterholes – and its mineral wealth. Today, the Pilbara is also dotted with gigantic, bright yellow robots – autonomous 500-tonne iron ore hauling tip trucks that make the Toyota LandCruisers they drive past look like Tonka toys, their rooflines barely half-way up the tip-trucks' wheels.

Durrant-Whyte became interested in Australia soon after his first forays with dockside robots while at Oxford. ‘If you are going to do field robotics, Australia is arguably the best place to do it. It is big and empty, and its economy primarily runs on things that sit in the back of large vehicles,' he explains. ‘So I moved to Australia.'

Australia's mining industry also had the financial muscle to lift the concept off the drawing board. It's now more than five years since the radar eyes of the Pilbara's first robot blinked open, took in its surroundings at Rio Tinto's West Angelas iron ore mine and then got to work – hauling ore from where it is dug up to where it is crushed, before being loaded on to trains and taken to the coast for export. ‘We've moved 200 million tonnes on the back of these autonomous trucks,' says John McGagh, head of innovation at the multinational mining giant. ‘By weight, that's equivalent to about 3500 Sydney Harbour bridges.'

Mining robots were not the first robots that Durrant-Whyte deployed in Australia. ‘As luck would have it, one of the first people I bumped into was Chris Corrigan, who was already running a container terminal,' he recalls. At the time, Corrigan ran Sydney-based logistics company Patrick Corporation. Durrant-Whyte was drawn to revisiting a dockside robot. ‘It's always good to do something a second time, because you've learned all the errors from last time. So we kicked off a program with them.'

From that meeting the AutoStrads were born.

* * * * *

It's hard to think of a better proving ground for outdoor robots than a shipping container terminal. The environment is structured, contained, relatively small and the robot's task is to move boxes from A to B. ‘In theory at least it seemed like a plausible problem to solve,' Durrant-Whyte says. Working out how a
machine as large as a straddle truck should move autonomously was one challenge, but the far bigger issue was sensor technology, and the ‘perception problem'. How does a field robot detect its surroundings and understand its environment well enough to go about a task safely and effectively? Inside, lighting is controlled. But outside the sun is constantly moving, clouds come and go, shadows shift. And then there's wind, rain, dust, or even snow and fog – all affect a robot's view of the world.

When it came to designing the AutoStrad's eyes, the research team were up against some tight constraints. When a 65-tonne truck loaded with a 50-tonne container is navigating the narrow confines of a busy shipping terminal, a positioning error of a few centimetres could be catastrophic. The team quickly ruled out the technologies most often used for artificial eyes: GPS and lasers. The reflective metal surfaces that fill a container terminal bounce satellite signals around and can derail GPS tracking. And lasers and optical cameras are fairweather friends – they can't penetrate far enough through rain. The team opted for highfrequency radar. The longer wavelengths don't get disrupted by raindrops, and to improve positioning accuracy, passive radar reflectors were stationed around the site.

The AutoStrads know where these reflectors are and triangulate their own position. But no individual sensor technology is foolproof, says Durrant-Whyte. ‘The challenge with a vision system is to know when it has failed. Think of your own vision system, sometimes it does fail, so you need an alternative way of detecting the object that will not fail in the same way,' he says. You might not spot the approaching motorcycle as you step out to cross the road, but your ears will pick up the buzz of its engine, and so you look again. And all the while, to keep us stable and upright, our brains are cross-checking information from our eyes with inertia sensors in our ears, and the sensation in our legs – which is why striding along a moving walkway can feel so peculiar.