Siouxsie Wiles is a microbiologist with a fascination for pathogenic bacteria. We live surrounded by constantly evolving enemies, she notes, which are continuously adapting to their environment, whether it’s on an animal, on a human or in a hospital. One in three human deaths worldwide is caused by a micro-organism, she says, and growing antibiotic resistance means the percentage will increase.
Wiles is also attracted to bioluminescence: the capacity of some animals – glow worms, angler fish, fireflies – to emit light, usually to attract a mate or scare off predators or lure in potential prey. In her job, at the University of Auckland, and as head of the Bioluminescent Superbugs Group, she has found a way to combine both enthusiasms to help find new drugs to treat some of the most lethal bacteria that afflict us.
She does this by developing glow-in-the-dark bacteria – that is, bacteria that have been tagged with the genes that enable bioluminescence. Why? As light travels through flesh, she and her colleagues can then inject the bacteria into animals and, with a camera, trace the impact of certain drugs on the bacteria in vivo.
This is an efficient way of doing things. Wiles doesn’t need to grow the bacteria in a petri dish, which (in the case of Mycobacterium tuberculosis, one Wiles’s pathogens of interest) could take weeks and months. She and her colleagues no longer have to physically count the bacteria, either; once they have established the relationship between the light levels and bacterial numbers, things are relatively simple. “The more bacteria there are, the more light there is.”
Of course, things are not quite so simple. Not all bacteria can be easily modified with a bioluminescent gene, and Wiles has tried to modify some bacteria without success. But those she has modified can be used on all sorts of creatures, such as rats, mice and zebra fish. For instance, she is starting a study using caterpillars (they’re cheap and can be bought over the internet) that will be infected with strains of Staphylococcus aureus. The aim is to get a better understanding of that bacteria, which causes a number of skin infections, is antibiotic-resistant and has a particular grip in New Zealand.
What can a caterpillar reveal about the impact of S aureus on Homo sapiens? The immune system comprises the innate immune system, the first line of defence that defends the host from infection by other organisms in a generic way, and the adaptive immune system, which confers protective immunity to the host. “But we share the first line of response with pretty much everything else. So if we’re looking at that, we don’t need to use an animal with a full immune system. We can use a caterpillar.”
Underpinning Wiles’s approach is her ongoing effort to develop scientific models that minimise the use of and effect on animals in the lab. It’s not that she is against using rats and mice (in a humane way), but keen to develop alternatives when possible.
In 2006, when she was at Imperial College London, Wiles was awarded the inaugural Replacement, Refinement and Reduction (3Rs) award, which rewards research that replaces, refines and reduces the use of animals in scientific research. This was for a study in which she looked at how a strain of E coli infected the body; she worked out a way to infect the mice naturally so she didn’t have to use the more common method, which involved inserting a needle down the rodent’s throat under anaesthetic. One British newspaper called it the “being nice to mice” award. Last year she was again awarded a 3Rs award, this time by the New Zealand National Animal Ethics Advisory Committee.
Wiles’s approach has even led her to replace mice with ham. A common way to work out how many bacteria are needed before light can be detected is to inject the bacteria into a dead mouse. “That’s a ridiculous use of a mouse. So I use ham. It’s a good colour, you can make slices of uniform thickness, it’s cheaper than steak.” And yet, she has struggled to get her work with ham published – “because it’s ham” – but she is still aiming for publication in one of the top journals.
Although the study might point out the blindingly obvious, the blindingly obvious is often overlooked. “It’s too simple. But anything that can promote a replacement to animals should be applauded.”
BEREAVED AT GREATER RISK
The risk of a heart attack escalates in the days and weeks after losing a loved one, according to a study in American Heart Association journal Circulation. It found that the heart attack risk was 21 times higher than normal in the day after a loved one’s death, was six times higher within the first week and declined steadily over the following month. Researchers say the study highlights the need for the bereaved, their friends and family, and health-care providers to be alert to this heightened risk.
THE RHYTHM OF LIFE
Sustained disruption to circadian rhythms leads to a shorter lifespan, neurodegeneration and impaired mobility, at least in fruit flies, according to a study in Neurobiology of Disease. The circadian clock is a mechanism tuned to a 24-hour-cycle that governs much of life on Earth, at a molecular, cellular, physiological and behavioural level. Although the study involved fruit flies, scientists say there are close parallels between them and us, that some of the genes regulating circadian rhythms in flies have been preserved through millions of years and that these genes do the same thing in humans.
A comprehensive investigation, laid out in a 60,000-page report, by the University of Connecticut has concluded one of its researchers, who came to prominence for his work with resveratrol, was guilty of 145 counts of fabrication or falsification of data. Resveratrol is found in grape skins, peanuts and some berries and is thought to confer health benefits. It’s unclear what impact the report will have on resveratrol research.