In April 2016, only two months after the World Health Organization officially declared the Zika virus outbreak a Public Health Emergency of International Concern, a team of Australian experts in tropical medicine and mosquito-transmitted diseases travelled to Brazil and Colombia.
Among the delegation, arranged by the Australian Trade and Investment Commission, was Associate Professor Joanne Macdonald from the University of the Sunshine Coast (USC) in Queensland. The molecular engineer, who also holds an appointment at Columbia University in New York City, has been developing point-of-care biosensors, similar to take-home pregnancy tests, to diagnose diseases. Importantly, these devices can rapidly detect the genomes of multiple diseases simultaneously, keeping costs down for diagnostic testing in areas where lots of diseases are co-occurring.
With A$130,000 from the Bill and Melinda Gates Foundation, she and colleagues in Queensland have been working on a proof-of-concept to test mosquitoes for malaria, dengue and chikungunya. The test will also detect the bacterium Wolbachia. When introduced into Aedes aegypti mosquitoes, this potential control agent has been found to prevent viruses, including dengue and Zika, from being transmitted to people.
Improving diagnosis during epidemics
A/Prof Joanne Macdonald (far right) and colleagues observing vaccine and antidote production facilities at the Institute of Butantan, Sao Paulo (Credit: A/Prof Joanne Macdonald)
In Rio de Janeiro, Macdonald heard from local researchers how diagnostic testing labs were overwhelmed by the Zika virus epidemic. Clinics were only testing pregnant women, she was told, and results were taking up to two weeks to be returned. Furthermore, labs were having difficulty distinguishing between Zika and dengue, which are closely related, she says.
In this environment, Macdonald’s biosensors could be a game-changer. Apart from reagent substances, which trigger chemical reactions that ‘amplify’ DNA to detectable levels, the tests only require the most basic of lab equipment: a heating block and centrifuge (a piece of laboratory equipment, driven by a motor that spins liquid samples at high speed). This means tests can be easily performed in a doctor’s clinic or hospital with results returned inside an hour.
“The scientists in Colombia and Brazil wanted the technology right then and there because there was such a dire need with the Zika outbreak,” she says.
Since the trip, Macdonald has begun working on a test to specifically detect the genetic signature of the Zika virus, eliminating the potential for inconclusive results. Having already developed tests to detect Ebola, Japanese encephalitis, West Nile virus, and Hendra virus, which has killed nearly 100 horses in Australia over the last 23 years, Macdonald is confident it’s within reach.
In a world where deadly disease vectors are increasingly mobile thanks to global transportation networks, Macdonald’s biosensors could become an important line of defence for future epidemics.
“If we can provide solutions that allow testing to be done at the point-of-care, rather than in a central lab, that would be a big help,” Macdonald says.
Macdonald has founded a startup called BioCifer to hold the intellectual property rights and commercialise the various technologies, and is currently working with USC to access the relevant intellectual property. With keen investors already in place, she’s hopeful a diagnostic product – initially for use in veterinary clinics and for research-only purposes – could be just two years away.
Rapid detection vital to saving lives
Reproducing the detection sensitivity of state-of-the-art labs in a cost-effective, portable device is the ultimate goal of Macdonald’s research, and though it may be a decade away, she is making headway. In December 2015, she and her then PhD student Jia Li reported a world-first milestone in the journal Lab on a Chip, published by the Royal Society of Chemistry.
They had developed a handheld, pregnancy test-style biosensor, which could detect up to seven different analytes, or theoretical diseases. What’s even more innovative is how the device notifies the end-user of the result: if DNA from a certain disease is detected it will light-up patterns of corresponding molecules or dots, like pixels on a computer screen.
Inspired by the seven segment displays on digital watches, the dots are arranged to resemble the numbers 0 through 9. It’s the first time a numeric display like this has ever been demonstrated on a paper-based biosensor, known as a lateral flow device, and amazingly, it requires no external power source.
The biosensor “is powered entirely by molecules,” says Macdonald. “We are borrowing from computing, but using molecules instead of computer bits.”
Programmed molecules play strategy games and make autonomous decisions
In 2006, while at Columbia University full-time, Macdonald and her colleagues built a computer out of DNA molecules. They programmed the DNA, modifying it to respond to stimulus, in order to play the strategy game tic-tac-toe interactively against a human.
In the future, programmed molecules could be used to develop biological machines that operate inside the body, releasing drugs or insulin autonomously, on demand – something her US-based colleagues are working toward. Macdonald, is harnessing the capability of this technology to more rapidly detect deadly diseases.
By embedding computing principles in molecules “we can decide whether they will turn on or off depending on the presence of other molecules around them,” she says. “So it’s like a chemical reaction based on logic, the molecules can make decisions on their own without any external inputs. And we pre-program them to do this.” This is how the dots in the biosensor know to light up.
Macdonald inside a laboratory at the Instituto Colombiano de Medicina Tropical, Medellin, Colombia (Colombian Tropical Medicine Institute)(Credit: A/Prof Joanne Macdonald)
Catching the microbiology bug
A rare illness in high school called coxsackievirus, which affected Macdonald’s heart muscles and prevented her from participating in sport, helped spur a lifelong fascination with disease. After she recovered, her interest blossomed at the University of Queensland. While there she majored in biochemistry and microbiology, and later completed a PhD investigating the West Nile virus under the supervision of immunoassay expert Professor Roy A. Hall, who she is still collaborating with.
Macdonald went on to spend 10 years at Columbia University, first in the lab of Professor Ian W. Lipkin, an epidemiologist who was the scientific adviser for the Hollywood blockbuster Contagion, and then working with two “humongous scientific minds” in Professors Donald W. Landry and Milan N. Stojanovic. Under their guidance she not only programmed DNA molecules to play tic-tac-toe, but also helped develop a drug that inactivates cocaine, which is now being trialled as a treatment for overdoses.
Back in Australia since 2012 and focused primarily on rapid disease detection, Macdonald is thinking about the next big question as point-of-care and biosensor technologies advance: “Can we actually predict epidemics before they start?”
In the future, she wants her biosensors to effectively act as shields, used pre-emptively by aid agencies and community members to screen their surroundings, including potential hosts of infectious diseases such as bats, monkeys and mosquitoes, before outbreaks occur. She hopes it might empower communities, enabling them to take precautions before they get sick, and ultimately save lives.