From a South African laboratory to global gamechange; the Gene Xpert test

The development in a South Africa laboratory of accurate controls to help in the battle against tuberculosis and the corona virus is a global success story.

It is imperative that testing for these diseases be done at speed, as accurately as possible and in significant quantities. To ensure that this diagnostic testing is done correctly, control materials are required which are live disease causing agents such as living corona virus or TB bacteria. However, these organisms are infectious and cannot be used in a widespread manner to verify diagnostics.

Enter Professor Bavesh Kana (above), together with his Biomimicry Diagnostic Verification Controls team at the DSI/NRF Centre of Excellence for Biomedical TB Research at the University of the Witwatersrand. They developed a suite of biomimicry-based controls where harmless bacteria were modified to include target genetic elements from organisms such as TB and SARS-CoV-2, thus mimicking them in testing platforms. This enabled verification of tuberculosis and CoVID-19 diagnostics across South Africa which are also now widely used on the international marketplace.

Professor Kana revealed that the TB diagnostics kit has been endorsed by both the World Health Organisation (WHO) and The Centers for Disease Control and Prevention (CDC) and is being used for testing in 51 countries for TB and 34 countries for corona viruses.

The team were also among the winners of the 2020/2021 NSTF-South32 Awards, known as the “Science Oscars” of South Africa, taking the award in the Innovation: Corporate Organisation category for their biomimicry-based controls.

At the Executive Leadership Workshop (ELW) that was hosted by Universities South Africa’s Entrepreneurship Development in Higher Education (EDHE) programme in Cape Town last week, Professor Kana presented his work as a Case study of successful research commercialisation. In attendance were deputy vice-chancellors as well as executive directors and directors heading up programmes responsible for entrepreneurship development, who also influence strategy and policy development at public universities.

The purpose of the ELW is to grow the number of institutions positioned as entrepreneurial universities and provide an opportunity for deputy vice-chancellors and other executive leaders in entrepreneurship development, to engage on entrepreneurship at universities, specifically as it relates to university strategy and policy. This year’s ELW, the fourth edition since 2029, was themed Commercialisatgion of Research. The ELW is sponsored by the British Council as part of its support to growing entrepreneurial universities in the South African ecosystem.

“When we talk of testing for this virus, we think of labs and test results received on a mobile phone – what we call the front end of the process. The question is, how do you know if your results are right and not mixed up with another specimen? There are thousands of these tests done every day and the labs are overwhelmed,” he explained.

“This is where our innovation comes in,” said Professor Kana. “For any lab to operate they need quality assurance systems, good sample handling and proficiency testing. For example, to confirm that a CoVID-19 test works, they put a known amount of the virus into the system, and if the diagnostic tests the expected result, the lab can operate with confidence that patient swabs will be processed through a high-quality workflow. However, to do this, you need a specimen with live CoVID-19 virus and you need to send this live sample out to laboratories, which is a dangerous prospect. The labs were stuck — how could they implement process controls without dealing with the live virus?”

The solution proved to be simple, safe and effective.

The team took a soil dwelling bacterium that is not dangerous or infectious, and they engineered small bits of the virus genome into this bacterium. Together with a local company, SmartSpot Quality CC, the team put this bacterium onto small pieces of paper with some dye to create a dried culture spot that can be used by the laboratories to determine if their TB or Covid-19 tests are operating as expected.

This also creates numerous opportunities to develop a diverse product range. The technology is protected through patents in various jurisdictions.

Professor Kana titled his presentation Democratising Access to Diagnostics because he believes that, no matter where you live or where you come from, you have the right to access world class diagnostics. “That’s been the primary driving force of everything that we do. South Africa is home to the world’s worst TB epidemic, a lot of it driven by HIV in terms of numbers. TB has also suffered notoriously from a lack of sufficient investment because it is the disease of the poor. It may surprise you to know that, until recently, we use TB diagnostic tests that were over 100 years old simply because this was not an area companies wanted to invest in.”

He explained how the Gene Xpert test for tuberculosis was introduced around a decade ago and proved to be a gamechanger. It reveals whether a person is infected with TB and also if the TB bacterium of the person is resistant to TB drugs such as rifampicin. The results are available in two hours as opposed to the previous 42 days with the old tests.

It was to be introduced around South Africa but the roll-out stalled because there was no quality control programme.

“We were asked if we could help. A good control is the actual organism but we couldn’t send the TB bacteria to all these sites to prove that the device worked. It was dangerous and would make people sick. I like simple. And so I thought we have to fool this device. And so we came up with the idea of using biomimicry.”

And so began the journey where safe bacteria were modified to include target genetic elements from tuberculosis organisms. The rest, as they say, is history.

Professor Kana had some wisdom for scientists and researchers:  “Seek simple solutions! And remember that the minute you think are done, there is a storm on the horizon,” he said.

“Once we had the product working, we ran into problems with scalability and the cost of production which was reasonably high. You have countries who are barely making enough money to get into the programme to do the diagnostics and then you add more money for a quality assurance programme which makes it too expensive for them. We also had to deal with biosafety issues as well as delivery delays. These were just some of the problems we had to contend with and overcome.”

“We needed help from our tech transfer office regarding patent and legal issues and we certainly wouldn’t have got to marketplace timeously without them. Having a product is great but you have to imagine it in its environment. At first, once we had perfected it, there were many people getting it for free and a colleague came to me and said, ‘You are not the Robin Hood of science’ and so we had to develop a business model and a company. We also had wonderful support from our university leadership. I always say, if you are enabled, you can do.”

The product rolled out around South Africa, into the African diaspora and eventually around the globe.

“This is a South African university and a South African laboratory that now helps all of these 51 countries with a TB programme. It has been incredibly humbling. Then CoVID-19 came and turned the entire diagnostic value chain on its head. We were approached early in 2019 to make controls to allow the quick rollout of CoVID testing.”

Professor Kana and his team are currently working on biomimicry-based controls for HIV, Hepatitis C-virus (HCV), the methicillin resistant staphylococcus aureus (MRSA) infection and leukaemia.

He emphasised that the success of their laboratory hinged on a well-funded research programme.

“Seed funding is important but it is not enough. We were able to be successful because we had a broad portfolio of funders who gave us a space to translate our research into something that was more meaningful and could grow.”

He shared some advice: “We had to always make sure that we had well-articulated needs. I have yet to come across a researcher who thinks he is doing irrelevant work. The question is how do you articulate that towards a specific need? If you step in and facilitate that type of conversation and that type of thinking, I think you’ll break the back of this entrepreneurship blockade which often defines universities.

“You have to hold the market close. You can’t develop a product in a silo; you have to imagine where it’s actually going,” he continued.

“When it comes to university environments and innovation, we live on this publish or perish paradigm. Our university culture is deeply entrenched and it’s not in the way research is done and monetised. Universities get money from the Department of Higher Education and Training for all the papers they publish and they get money for all the students who graduate. Their business model is fundamentally linked to this value system. And this value system has little to no place for innovation.”

He also emphasised that researchers and scientists should not be defined by the resources available to them, describing how a few years ago the ceiling of his lab collapsed and was held in place by wire hangars.

“Your environment does not define you; your resources do not define you. What defines you is your thinking and your attitude to what you can do. Create meaning and lead by example. And never think that we don’t have home-grown talent,” he reiterated, paying tribute to two of his students – Moagi Shaku who has developed the first South African home-grown modified BCG vaccine and Itumeleng Boshielo who has developed a biomarker signature for POC diagnostics. Both students came from the University of Limpopo.

“They have developed a level of entrepreneur acumen that I believe is enviable. We need to separate myths from facts. Is there talent out there? Yes. Can it be done? Yes. Is it easy? No. Is it worth it? Yes.”

Professor Kana paid tribute to his team of researchers and enablers, including Dr Edith Machowski, Dr Christopher Ealand, Dr Bhavna Gordhan, Dr Dale Liebenberg, Dean Sher, Anest Reyneke, Chyreene Truluck and Tyron Grant as well as Ela Romanovska, Eleni Flack-Davison,  Zeblon Vilikazi and Robin Drennan. He emphasised the need to build partnerships outside of the academic space.

Janine Greenleaf Walker is a contract writer for Universities South Africa.