Cracking the code

Two Stellenbosch University researchers are pioneering a finger-prick test for the early detection of cancer.  JANNA JOSEPH finds out how they did it, how it works and how it could change the world.

Vasco de Gama. Marco Polo. Christopher Columbus. Famous names that conjure images of crashing waves, creaking ships and untouched, craggy coastlines. There’s something thrilling about standing at the forefront of what is known and discovering something new.

Just ask Professor Resia Pretorius and Professor Willie Perold. They may wield microscopes instead of telescopes and wear white lab coats instead of windswept cloaks, but these modern-day voyagers are just as intrepid as the explorers of old, venturing forth into uncharted new worlds – worlds hidden beneath the human skin.

Their latest destination? A molecule in the blood called serum amyloid A (SAA), a seemingly insignificant protein made suddenly significant by its ability to signal cancer in the very early stages of the disease.

Sian Bradbury, Este Burger and Riaan Laubscher.

Portrait of a protein

“If someone has cancer, you will be able to detect higher and higher levels of SAA in their bloodstream and this will happen years before any other signs or complications have developed,” says Resia, who is the head of Stellenbosch University’s Department of Physiological Sciences. “SAA becomes seriously upregulated in many inflammatory conditions, but this effect is particularly pronounced in cancer, where a person’s SAA levels can be up to 1 000 times higher than usual.”

Every inflammatory condition – from cancer to diabetes and dementia – has a profile of associated ‘inflammatory markers’, which are specific proteins that become upregulated, or are produced in higher amounts, when you have that condition.

“Every disease has its own inflammatory profile or footprint, which is characterised by different markers,” Resia explains. “We have been studying various inflammatory molecules in order to identify different disease profiles, new treatment regimes and early identification techniques.”

The result? A revolutionary finger-prick test for SAA – and, therefore, cancer – with the potential to save many lives in Africa’s most underprivileged areas.

“There are no pathology labs in rural Africa,” continues Resia, “so a large number of people with cancer are currently being diagnosed only when they’re in stage 3 or 4, when the World Health Organisation says they can’t be treated because they won’t survive anyway. So the idea is to try to identify these people much earlier, using our biosensor as a simple, affordable screening test. If a problem shows up, that person could then be sent for further testing and life-saving treatment.”

Patented with renowned cancer researcher Professor Anna-Mart Engelbrecht, Professor Perold and Professor Wim de Villiers, the new biosensor is just one of many breakthroughs for Resia, who received the prestigious Department of Science and Technology’s Women in Science Award in 2017, followed by the NSTF Award in 2018 (these awards are referred to as the ‘Science Oscars of South Africa’). The whiteboard in her office at Stellenbosch University stands testimony to her achievements, boasting an impressive list of previously and soon-to-be-published articles in top international journals.

Resia knows only too well the body is a complex, interactive system, but that early detection of disease is often a simple matter of knowing what to look for. “People often say, ‘Oh, Mary just suddenly had a heart attack’ or ‘John was so healthy and then he suddenly got cancer’. But you don’t just suddenly develop something out of the blue,” she says with a smile. “It builds up over years or months, based on your lifestyle choices, your genetic predispositions and many other tiny changes inside your body. SAA upregulation is one of those changes and we can use it as an early marker of inflammatory disease.”

Engineering the answer

Once Resia and her team of students had identified SAA as a reliable cancer marker, they needed the help of Professor Willie Perold, an electronics engineer in Stellenbosch University’s Department of Electrical and Electronic Engineering.

“I was still working in Pretoria when Willie and I first spoke,” she recalls. “I had the inflammatory data and he had the background with nanosensors and we thought, ‘What can we do?’” The duo planned the entire project in just a few months and Resia moved to Stellenbosch University in January 2017.

“Willie makes nanobiosensors, which can detect the levels of specific molecules in a drop of liquid,” she explains. “Essentially, he prints a tiny electrical circuit on a strip of paper, along with a specific area that can bind to (or hold onto) the molecule of interest.”

In the case of SAA, this area contains antibodies for the protein SAA. Antibodies are the body’s made-to-measure hitmen: if an intruder enters your bloodstream – be it a virus, a bacterium or a foreign molecule – your immune system will produce specific antibodies to identify and bind to that particular intruder, marking it for destruction.

“When a drop of blood is placed on the nanosensor, the SAA will bind to the antibodies and change the resistance of the circuit,” explains Willie. “This change in resistance depends on the concentration of the marker in the blood and it can be measured.”

Willie and his students print the strips using a conventional inkjet printer, which they have modified substantially. “It had to be carefully engineered to make sure the alignment of each substance is spot-on,” he says. “You also have to use a good paper that won’t let the substances you’re printing run or spread, and you have to mix your own specific ‘inks’. We used a solution of silver nanoparticles – at just the right viscosity – to create the conductive layers, as well as a semi-conductive polymer layer, where the biorecognition element goes.”

The result: a simple testing strip which is easy to use and cheap to produce, costing as little as R2 per test. Like the device used to read a diabetic’s blood-sugar levels, the strip will be inserted into a digital reader, which will provide the result within minutes.

“It’s an exceptionally simple idea,” says Willie. “You have a generic reader, which can be calibrated to detect whatever molecule you’re interested in. Then you take your specific strip with the right biorecognition element – such as antibodies for SAA – pop a drop of blood on it and get your result.”

The two professors and their students are also working on several additional nanobiosensors that will ultimately be able to detect many different molecules of interest. Thus, by combining their skills, the researchers have created a team that is truly greater than the sum of its parts.

“If you want to solve real-world problems, you need a multidisci­plinary team,” says Willie. “Society’s problems lie in the spaces where different disciplines meet and that’s where the solutions lie, too.”

The next steps

Having secured funding from the Technology Innovation Agency (TIA) and Innovus – Stellenbosch University’s industry interaction and innovation company – Resia has a clear plan of action.

“We hope to have a pre-prototype of the sensor in our hands by the end of 2018,” she says. “We will then test it using the samples we already have here in the lab. After that, an independent pharmaceutical company will need to buy the sensor and put it into production for further testing. The results of those independent tests will need to be approved by the FDA so that the product can be rolled out for use in the field.”

Within a few years, the nanosensor could be actively detecting cancer in every mobile clinic in Africa. It could also be used in state-of-the-art hospitals, says Resia, where it could play an instrumental role in gathering data and tracking patients’ progress. Patients could even take the reader home and test their own levels each month, uploading their results to a central database for long-term monitoring.

“We want to change the world,” says Resia, a sparkle in her eye. “We want to facilitate the early detection of disease. We want to treat people before they are sick or, at least, before they’re too sick to be treated. And we want to do it cheaply, so that every mobile clinic in Africa can have access.”

It’s a distant horizon, but it’s a horizon filled with promise and when you’re on a voyage of discovery, there’s really no better sign than that. V