Africa could lead the way in precision medicine

Long before you have a heart attack, long before you develop a malignant tumour, long before you experience the first tremor from Parkinson’s, your immune system has swung into action. 

To defend against the impending threat of which you are still blissfully 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. They are the biological markers that reveal the presence of a condition or disease, long before any actual symptoms show. 

One of the best known and 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 far more reliable than the – now mercifully obsolete – invasive digital rectal examination (featuring the infamous gloved finger).

But while the PSA test is now commonplace and accurate, there is at present no early warning for many other highly dangerous dread diseases – specifically lung and breast cancer. 

Lung cancer, for example, is almost never detected until Stage 3 or 4 because it can advance without any symptoms or pain. By the time these manifest, the cancer has usually metastasised (spread to other body organs). Breast cancer and ovarian cancer are also seldom detected until there is already a mass. 

Your body fights cancer all the time. Every day, 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 continue to grow uncontrollably. But if they do, the levels of antigens and autoantibodies in the blood reveal their presence. 

These are the tests – among several others – that Philani Mashazi, Associate Professor of Inorganic and Analytical Chemistry at Rhodes University, is working on. His cutting-edge work in this field of study won him Rhodes University’s Vice-Chancellor’s Distinguished Research Award for 2021.

x=x=-Prof Mashazi. Image: Chris Marais

Detection in a nano world

Antigens and autoantibodies are unimaginably tiny. They are minuscule assemblages of specific proteins “folded” into characteristic shapes. If you were to shrink yourself down to the nano size of one of these antibodies, the width of a human hair might seem as high as Mount Everest.

Not surprisingly, 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 in one place. Currently they are in the Department of Chemistry, but ground has been broken on a new building that will house them 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 that indicate looming health issues. 

It is possible not only to detect cancer antigens, but also to reveal how far the cancer has advanced, from Stage 0 to Stage 4. These are mighty tools in the hands of oncologists.

The young man from Nqutu

While growing up in the rural lands around Nqutu in KwaZulu-Natal, Philani Mashazi did not for a moment dream of becoming a professor in chemistry, teaching lecture halls full of young students and supervising postgraduates.

“Back then, I had been exposed to only three professions,” he says. “I could become a teacher, or a nurse, or a policeman like my father. And if all else failed, I could fall back on being a taxi driver.”

Philani encountered chemistry in school, but there was no laboratory, so it was all theoretical. By his matric year, in the late 1990s, his grasp of English was still rudimentary – “We studied English in isiZulu,” as he puts it – but he achieved fairly good marks in most subjects. Encouraged by his maths teacher, young Philani sent in applications to tertiary institutions around the country.

The first positive response came from Rhodes University.

“That quick response made me feel wanted and valued. But no one in my village had any idea where the university was.”

Just getting to Grahamstown, now Makhanda, was a terrifying journey, helped somewhat by the fact that Philani’s father was a policeman at Johannesburg International Airport – now OR Tambo Airport.

“I only knew one way to get there – by plane to Port Elizabeth. My dad told me exactly what to do and I followed his instructions to the letter.”

Once at Rhodes, settling into Adamson House residence, Philani realised what an uphill battle awaited him. 

Finding a passion

“I could still barely speak English, and only one other student there spoke isiZulu. Fortunately, I could do a bridging course for English and I did extended studies too. They introduce you, slowly, to some of the courses that you are going to be doing.” 

Once he settled into Chemistry, Philani realised he had found his academic home.

“As you advance in your education, you find a subject that speaks to you. Chemistry was that for me. You could wake me up in the middle of the night and say, ‘Here’s a chemistry test’, [and] I wouldn’t fail it.”

For his Honours degree, Philani plunged further into Chemistry under the supervision of department legend, Distinguished Professor Tebello Nyokong.

“From the moment I stepped into her lab (S22) and witnessed how excited her students were to be doing research, I wanted to be part of that excitement,” he says.

With his Honours behind him, Philani reached a fork in the road familiar to many students. He was keen to carry on studying, but his family began to exert pressure on him to find a job. So he tried. He headed off to Johannesburg, sent out his CV, shadowed people at work and went for dozens of job interviews with no success.

“Then my dad said, right, what is Plan B? The only Plan B I could think of was getting a bursary for my Masters. I contacted Professor Nyokong, and she promised to figure something out. There was no money for planes, so this time my dad paid for a one-way train ticket to Grahamstown. I arrived with nowhere to stay, no funding at all. I headed straight for her office.

“I was awarded a small bursary and a stipend for tutoring and lab demonstrations for first-year students, generally assisting the academics, marking papers and so on. It was just enough for a really cheap rent and basic food. I found student accommodation near Kingswood. It was a tiny room, basically a pantry. The only furniture that fitted was a single bed.”

Precious metals 

Metals like gold and palladium help to make diagnostic equipment more accurate and sensitive, says Professor Mashazi. 

During his Master of Science (MSc) degree at Rhodes University, he worked on electro-chemical sensors, some of which included precious metals. His work attracted the attention of Mintek, the national mineral research oganisation. They offered young Philani a bursary with running costs, and the promise of a job after he graduated with his MSc.

“It was an absolute dream come true,” says Mashazi. He had been surviving on a hand-to-mouth budget, but with a bursary, he could move to more spacious digs than the little pantry. 

He, however, decided to remain there, “save my money and devote my life to study”.

Atomic resolution in Ghent

During his Masters studies, Mashazi experienced a four-month exchange programme in Belgium. There he became somewhat addicted to Belgian foot-long sandwiches, and was exposed to nanoBiosensor research equipment for the first time.

“I saw that they have access to XPS, Raman spectroscopy and the atomic force microscope. 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 in different places, often spread out over distant cities. 

“After I got home, the results were sent to me by email. I presented the data to my supervisor, Professor Tebello Nyokong, who was surprised about what we can see under these spectrometers, notably the Raman spectrometer and the [XPS]. Professor Nyokong was specifically interested in the fact that what was postulated could now be proven spectroscopically.”

Unbeknown to Mashazi at the time, Nyokong started to write proposals to acquire some of these specialised machines.

The lure of academia

Mashazi obtained his MSc with distinction, and headed off to Gauteng, where he began working at Mintek in 2007. Two years later, there was a massive national outbreak of measles in South Africa, with Gauteng as its epicentre. At the time, there was only one laboratory 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 and use that to get 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. He enjoyed the various challenges at Mintek, but eventually, he found the lure of academia too strong to resist.

“My mind was increasingly inclined towards knowledge generation, and imparting knowledge, not doing research because it’s going to make money in the short term.”

It was around then that he stumbled across an advert for the post of senior lecturer in the Chemistry Department at Rhodes University, and immediately applied. 

“I got the job and I was very happy. It’s one of those times where you think, ‘I wouldn’t trade this for anything’.”

Africa’s diverse genome

Mashazi loves working with his postgraduate students and postdoctoral fellows.  

“We are attracting researchers from all over the world. We’ve had students recently coming from Belgium to spend about four months with us, just to access the facilities that we have here at Rhodes University in the Institute for Nanotechnology Innovation. We have had researchers from Poland recently too. 

“In my current group, I’ve got a Malawian, a Zambian, Zimbabwean, and a number of South African students. I’m a strong believer that diversity brings excellence. In Professor Nyokong’s group, which I also work with, there are students from all over the continent of Africa.”

This is a critically important knowledge hub for the continent. As Mashazi explains: “Africa has a far more diverse genome than Europe and North America, where most drugs are developed and tested. What works on one continent might not work in Africa. We are looking at the patient-specific treatment and levels of toxicity, which is often indicated by weight loss and hair loss in cancer treatment. It’s becoming more and more important that we don’t just adopt medication. Instead, we get the regime, and then adjust it internally to see what works for the African continent. It really is very exciting.”

The ultimate dream

There is a scenario that Mashazi envisages over and over. It is that of individualised or precision medicine, where every individual has their levels of biological markers mapped. An annual visit to a doctor, 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 that your body is showing biochemical reactions that are producing certain molecules. You might be predisposed to a certain kind of cancer. Or a biomarker might show that a cardiac arrest is a real danger, long before you clutch your chest and fall to the ground. You can treat and monitor your health issues before they become a problem. You can lengthen and improve the quality of your life.

“This could transform doctor-patient relations. For me, that is 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. Obviously it will take some years, but I’m really looking forward to just seeing how the results are revealed, as we go through the research.

“So in an ideal world, each individual would have his or her own medical profile with their particular antigens, neurotransmitters and various biomarkers in their blood. And then you’d be able to see the spiking or sinking in terms of concentrations. This is what we need to do.”

Screening on paper

One of the most promising parts of his current research shows that detection could be done far more cheaply than is now the case.

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. 

Young professor, top university

During 2020, Mashazi was chosen as the Rhodes academic to take part in the Department of Higher Education and Training’s first Future Professors Programme. 

It has been a great honour, he says.

As he puts: “This is the opportunity I have been waiting for. I feel it will help me grow as a research scientist and my scholarly output will without a doubt increase.”

Being deputy director of the INI means straddling the fields of nanoBiosensors and Chemistry. Mashazi is extremely proud of the fact that Rhodes University is the top institution in South Africa, and among the leading universities in the world, in this cutting-edge field of nanotechnology and diagnostic medicine.

“Thanks to Professor Tebello Nyokong, Rhodes is unique in the world for having all these specialised pieces of equipment under one roof. It is one of our great selling points, and the reason we are attracting students from all over the world.” DM/ ML/MC

A version of this article first appeared in Rhodes University’s Research Report 2021, published in November 2022.