In the future, a few drops of your blood, saliva or tears could give you early warning of impending cancer, heart attacks or other dread diseases; possibly pre-empting medical emergencies and saving lives, says a local scientist, who says this field of ultra-sensitive disease diagnostics is already in the making.
Philani Mashazi, associate professor of Inorganic and Analytical Chemistry at Rhodes University, is right at the forefront of this innovative technology, explaining that long before you have a heart attack, develop a malignant tumour, or experience the first tremor from Parkinson’s, your immune system has swung into action.
To defend against the impending threat of which you are unaware, your body is creating highly specific autoantibodies from antigens or pathogens (body invaders), and other custom-made weapons for the battle under way at a molecular level.
Because they are so specific to cause, such a precise lock-and-key match between threat and defence, the autoantibodies are tiny but highly accurate red flags: the biological markers revealing the presence of a condition or disease, long before actual symptoms appear.
One of the most commonly used biomarkers is the Prostate Specific Antigen (PSA), which reveals the presence of prostate cancer.
Screening for PSA has, since the 1990s, contributed to a significant decline (between 45% and 70%) in age-adjusted prostate cancer mortality in most countries. It is also more reliable than the obsolete, invasive digital rectal examination.
In the Daily Maverick, Mashazi explains that while the PSA test is now commonplace and accurate, there is currently no early warning for many other dread diseases – specifically lung and breast cancer.
Lung cancer, for example, is seldom detected until stage three or four because it can advance without symptoms or pain. By then, the cancer has usually spread to other body organs. Breast cancer and ovarian cancer are also seldom detected until there is already a mass.
Your body fights cancer continuously. Daily, up to five cells in your body will turn cancerous, but your immune system corrals and kills them before they can multiply. Some eventually do manage to outwit the inner defence systems and grow uncontrollably. But if they do, the antigen and autoantibody levels in the blood reveal their presence.
These are the tests – among several others – on which Mashazi is working, his field of study having won him the 2021 Rhodes University’s Vice-Chancellor’s Distinguished Research Award.
Detection in a nano world
Antigens and autoantibodies are unimaginably tiny, minuscule assemblages of specific proteins “folded” into characteristic shapes. Unsurprisingly, the instruments needed to measure the chemical and biochemical traces and quantities of these nano-weapons must be delicate, custom made and ultra-precise.
Rhodes University is unique in the world for having six of these highly specialised pieces of equipment. They are in the Department of Chemistry, but ground has been broken on a new building where they will be housed under the auspices of the Institute for Nanotechnology Innovation (INI), of which Mashazi is deputy director.
These rare items of machinery include the transmission electron microscope and scanning electron microscope, the X-ray photoelectron spectroscopy (XPS), atomic force microscope, Raman spectroscopy and Time-of-Flight Secondary Ion Mass Spectroscopy.
From a tiny droplet of your blood, urine, tears or saliva, their nanotechnology-enabled biosensors (nanoBiosensors) can detect the antibodies indicating looming health issues, and not only detect cancer antigens, but also reveal how far the cancer has advanced, from stage sero to stage four.
Born in rural Nqutu, KwaZulu-Natal, Mashazi never imagined becoming a professor in chemistry.
“I had been exposed to only three professions,” he says. “I could become a teacher, or a nurse, or a policeman like my father.”
By matric, his English was still rudimentary but he achieved fairly good marks overall. His maths teacher encouraged him to apply to tertiary institutions countrywide.
The first positive response came from Rhodes University. “That made me feel valued. But no one in my village had any idea where the university was.”
Just getting to Grahamstown was terrifying, but once at Rhodes, in residence, Mashazi realised the uphill battle awaiting him.
Finding a passion
“I could barely speak English,” he said, but in chemistry, he found his academic home.
For his Honours degree, he plunged further into chemistry under the supervision of department legend, Distinguished Professor Tebello Nyokong.
With his Honours behind him, Mashazi reached a familiar fork in the road, keen to continue studying, but with his family exerting pressure on him to find a job. So he headed to Johannesburg, sending out his CV, having dozens of unsuccessful interviews.
“Then my dad asked what plan B was. I decided to get a bursary for my Masters. I contacted Prof Nyokong, and she promised to figure something out, so my dad paid for a one-way train ticket to Grahamstown.
“Luckily, I got a small bursary and stipend for tutoring and lab demonstrations for first-year students, generally assisting the academics, marking papers, etc. It was enough for cheap rent and basic food.”
Precious metals
While doing his Master of Science (MSc) degree at Rhodes, he worked on electro-chemical sensors, some of which included precious metals. Metals like gold and palladium help to make diagnostic equipment more accurate and sensitive, he says.
His work attracted the attention of Mintek, the national mineral research organisation, which offered him a bursary with running costs, and a job after graduating with his MSc.
During his Masters studies, he enjoyed a four-month exchange programme in Belgium, being exposed to nanoBiosensor research equipment for the first time.
“They have access to XPS, Raman spectroscopy and the atomic force microscope, and I realised how much they could assist my research in helping me to ‘see’ the interface surface of the biosensors at sub-molecular and atomic resolution.”
The logistics were not easy. With the help of his co-supervisors, Mashazi booked the use of the instruments within two weeks of his arrival at Ghent University. But the waiting list was long, and tests could only be run a week before he returned to South Africa.
The various machines were spread out over distant cities.
“After I got home, the results were emailed to me. I presented them to my supervisor, Prof Nyokong, who was surprised about what we can see under these spectrometers, notably the Raman spectrometer and the (XPS). She was specifically interested in the fact that what was postulated could now be proven spectroscopically.”
Unbeknown to Mashazi then, Nyokong started writing proposals to acquire some of these specialised machines.
The lure of academia
Mashazi obtained his MSc with distinction, and left for Gauteng to start working at Mintek in 2007. Two years later, South Africa saw a massive national measles outbreak, Gauteng being its epicentre. At the time, there was only one lab doing measles testing: the National Institute for Communicable Diseases.
“I found a way to diagnose the virus via electro-chemical tests, where you simply take a throat swab to use for a positive or negative result for measles. That became the subject of my PhD.”
By 2013, Mashazi had successfully graduated with his doctorate while working full time at Mintek, but found the lure of academia too strong to resist.
He saw an advert for a senior lecturer in the Chemistry Department at Rhodes University, and immediately applied. “I got the job and I wouldn’t trade this for anything.”
Africa’s diverse genome
He says the department attracts researchers from all over the world, and is a critically important knowledge hub for the continent.
“Africa has a far more diverse genome than Europe and North America, where most drugs are developed and tested. What works there might not work in Africa. We look at the patient-specific treatment and levels of toxicity, often indicated by weight loss and hair loss in cancer treatment. It’s becoming increasingly important that we don’t just adopt medication. Instead, we get the regime, then adjust it internally to see what works for our continent.”
Mashazi envisages a scenario of individualised or precision medicine, where every individual has their levels of biological markers mapped. An annual GP visit, a few drops of blood, saliva or tears, and the doctor can see a real-life picture emerge of that person’s health.
“The doctor would tell you your body is showing biochemical reactions that are producing certain molecules. You might be predisposed to a certain cancer. Or a biomarker might show a cardiac arrest is a real danger, before you fall to the ground. You can treat and monitor health issues before they become a problem, lengthen and improve your quality of life.
“This could transform doctor-patient relations – for me, the most important. You would have someone look at your patient history and say, ‘We haven’t seen this kind of concentration in this particular biological molecule, but now it’s emanating as very important. How can we mitigate the risk?’
“It’s going to be revolutionary…but obviously will take years.
“So in an ideal world, people would have their own medical profiles with their particular antigens, neurotransmitters and various biomarkers in their blood. And you’d be able to see the spiking or sinking in terms of concentrations.”
Screening on paper
One of the most promising parts of his research shows that detection could be done more cheaply than it is.
Imagine a world where a few small drops of blood on a piece of paper, treated with embedded biosensors, could check your biomarkers and give you early warning of impending threats via a smartphone. For example, if a biomarker indicates that a heart attack is imminent, you could book yourself into a clinic for observation.
The possibilities, believes Mashazi, are endless.
Daily Maverick article – Africa could lead the way in precision medicine (Open access)
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