Traditional and mainstream medicine have long been at odds. But COVID-19 may be providing the impetus for the two sides to work together to explore the potential for plants used in traditional medicine to become an untapped pharmaceutical resource.
In June, Artemisia afra was in high demand on the streets of Johannesburg in South Africa. To treat COVID-19 symptoms, the Indigenous herb’s silvery leaves were for sale at roadside vendors and in the city’s popular traditional markets. Some people even pulled the plant from private gardens. And on the sides of nearby highways, people held signs for “mhlonyane” (A. afra’s isiZulu name) and offered bushels to passing motorists like bouquets. Between February and July, the herb doubled in price.
People in the region have consumed the bitter plant for centuries to treat illnesses from colds to intestinal worms. With deaths rising as South Africa battled its first COVID-19 wave, people have turned to A. afra and other traditional medicines, including cannabis. (They were not the only ones. In April, Madagascar’s president, Andry Rajoelina, had launched COVID-Organics, a herbal concoction containing another artemisia species, A. annua, which he claimed — without evidence — could cure COVID-19.)
As with most traditional medicine in South Africa — a broad category that relies on a variety of herbs, rather than the refined molecules of Western drugs — there is no robust, peer-reviewed evidence that A. afra has any utility against any ailment, including COVID-19. Local medical doctors and officials have cautioned the public against using the plant instead of seeking medical attention for COVID-19, and the World Health Organisation (WHO) has similarly urged people to avoid using untested medicines to treat the disease. But that has not stopped demand for A. afra — and that demand now has some mainstream health advocates calling for greater scrutiny of traditional remedies — including submitting them to clinical trials.
Whether this will come to pass is far from clear. Despite South Africa having a large number of practicing traditional healers and millions of mostly Black South Africans who use their medicines, traditional health care practices stand well outside of mainstream health care in the country. Although there have been efforts to regulate traditional healers, their remedies, for the most part, have not been subjected to scientific scrutiny. This is in part due to South Africa’s history. While people in the region have used traditional medicines for millennia, in 1957, the racist apartheid regime suppressed traditional healing through the Witchcraft Suppression Act, labelling many of its practices as criminal offenses and forcing it underground. There is also a long history elsewhere in the world of scientists and companies turning Indigenous knowledge into Western medicines, and many stakeholders fear that, once healers divulge their secrets and methods to expose their therapies to the rigour of clinical trials, this will happen again with South African traditional medicine.
Indeed, many herbal remedies are closely guarded secrets, intertwined with a philosophy in which health is inextricably linked with spiritual life. And unlike other ancient healthcare systems that rely on written texts, African healers share and preserve knowledge largely through oral tradition, so there is little record of how the medicines were made and used hundreds of years ago. This lack of ingredient information and recorded longitudinal safety data make African traditional medicines particularly difficult to test.
Still, the WHO and the Africa Centre for Disease Control and Prevention, in collaboration with the Developing Countries Clinical Trial Partnership (EDCTP), have developed guidelines to evaluate the medicines’ safety and efficacy against COVID-19. And while some experts lobbying for more scrutiny of traditional medicine noted that South Africa’s drug regulators have been historically antagonistic to the idea, the unprecedented COVID-19 pandemic may well be helping to change all that. Indeed, government overseers have established a special unit to evaluate these traditional products, and while answers may come too slowly to address COVID-19, the investigations may have long-lasting implications. “COVID has been a game changer for traditional medicine,” said Nceba Gqaleni, a traditional medicines specialist at the Africa Health Research Institute in Durban, adding that the COVID-19 treatments haven’t faced some of the same controversies as past traditional medicines — especially therapies for HIV/Aids.
A. afra is one of a number of herbs that the government is investigating against COVID-19. In July, officials set up the African Medicines COVID-19 Research Team, which includes scientists and traditional healers, and diverted about R15-million (at the time equalling about $880 500) from existing Indigenous knowledge projects to fund the collaboration.
The project could lead to other research outside of COVID-19, since the country is home to 10% of the world’s plant species and remains a largely untapped pharmaceutical resource. Nox Makunga, a medicinal botanist at Stellenbosch University, says that since the abolition of apartheid, the South African government has been expressing eagerness to investigate and develop effective herbal medicines. “They see it as ‘green gold,’” she said. But that hasn’t yet come to fruition. In 2008, the government published a draft policy for traditional medicines, which was subsequently shelved, and while South Africa’s 2013 Bioeconomy Strategy laid out ambitious plans to investigate herbal cures, the country has not yet managed to formally evaluate traditional medicines or discover any new drugs based on their constituents.
The COVID-19 pandemic may be providing new impetus for such efforts, but experts say it won’t happen without compromises.
Modern medicine, of course, hinges on the ability to show that any particular compound — be it from nature or synthetically-derived — is effective and safe at an established dose. Such demonstrations are generally obtained through clinical trials, and while the process is not without shortcomings, it has generally yielded tried, tested, and — importantly — reproducible results. “Clinical trials are the best and safest way” to evaluate medicines, said Francois Venter, deputy executive director of the Wits Reproductive Health and HIV Institute at the University of the Witwatersrand. The drugs are tested for safety in animals and humans, and this way of testing is widely accepted, he added. “But there are no shortcuts, they are expensive.”
This standardised approach, however, is at odds with the opaque and complex belief system that underpins African traditional medicines. “We are responsible for the body, the mind, and the soul,” said practicing healer Phephisile Maseko. “We are the only healing system that looks into all three, unlike Western medicine which just focuses on applying bandages.”
In this system, ancestral worship is intertwined with people’s health, and is just as important as the plant formulations a healer dispenses. When a patient comes to Maseko, she says she asks questions about not only people’s ailments, but also their histories: “‘What happened to your mother? Why is there no connection between your mother and the family of your father? What happened when you were born?’”
Similarly, when Hlupheka Chabalala, head of Indigenous knowledge-based technology innovation in South Africa’s department of science and innovation, refers to traditional medicines, it is typically a mixture of various whole-plant extracts, rather than single, isolated compounds. The different plants in the medicine work together, he suggests: One may act as the primary medicine, while another promotes the body’s absorption of the drug, or the bioavailability, and another might curb the side effects of the other plants.
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The importance of family history and the benefits of complementary drug interactions are, of course, not foreign to Western medicine. The problem is that formulations and ingredients in traditional cures vary widely, making most assertions of efficacy exceedingly difficult to prove — and leaving many experts dubious. “Most things are not safe if you get them from nature,” said Kelly Chibale, an organic chemist who heads a drug discovery group at the University of Cape Town. “They’re actually very toxic.”
But testing such custom-made, non-standard preparations can prove advantageous. “If you want to push biodiversity or African traditional medicine, you have to conduct a clinical trial, a clinical study, because that’s the only way scientifically you can prove something works,” said Chibale. He pointed to sweet wormwood (Artemisia annua), the cousin of A. afra used in COVID Organics and an important plant in Chinese traditional medicine: “For more than 2 000 years, the Chinese have been using that drug in a concoction, as part of traditional Chinese medicine.” It wasn’t until the 1970s, however, that Chinese scientists derived molecules from the feathery green A. annua, called artemisinins, that now form the cornerstone of malaria therapies around the world. Artemisinin-based combination therapies have more than halved annual malaria deaths globally.
That accomplishment required modern tactics. Scientists needed to understand the chemical structure of sweet wormwood in order to identify its active pharmaceutical ingredient, Chibale explained — and along the way they discovered it was poorly soluble and not absorbed well. Scientists were then able to chemically modify artemisinin to produce better-performing derivatives. In that sense, the traditional medicine served as the pathfinder for a drug that would save millions of lives — but modern science was needed to bring that about. “Everything is just a starting point,” Chibale said.
That notion, however, does not sit well with many traditional medicine proponents, including Chabalala, who says they should be considered an end to themselves, and not individually dissected to identify one active compound. “We use everything as nature intended it to be, even if mixing herbs,” he said. “If you isolate compounds, that’s when you start having problems with side effects.”
Venter, a proponent of evaluating traditional medicines via clinical trials, dismisses this as unscientific. “There is this idea that something natural is good for you, but heroin is natural,” he said. “I’d rather take a highly synthetic compound than chew a leaf that is going to give me heart failure.”
(While A. afra does not contain artemisinin, it has also been proposed as a treatment for malaria. According to the WHO, however, chemical compounds found in the plant can vary widely and concerns about damage to the brain and heart have been reported.)
Despite the South African government’s stated interest in developing drugs based on traditional cures, many people involved in traditional medicine, including Gqaleni, say South Africa’s Medicines Control Council (MCC) was historically reluctant. “They thought they were lowering their standards to approve traditional medicines,” Gqaleni said. But legislation to replace the MCC with the South African Health Products Regulatory Authority (Sahpra) was passed in 2015, and amid the pressures to find new ways to treat COVID-19, the agency has recently come to the table with traditional medicine advocates. Sahpra has “begun considering appropriate mechanisms of regulating proprietary African traditional medicines,” spokesperson Yuven Gounden told Undark.
Historically, traditional medicines research had not been scientifically rigorous, says Salim Abdool Karim, an infectious disease epidemiologist and the co-chair of South Africa’s Ministerial Advisory Committee on COVID-19. “So it has given traditional medicines research a bad name. But we shouldn’t let a few lapses in scientific quality put us off a fundamentally important issue.”
Scientists, public officials, and traditional healers all seem to agree that traditional medicines must be shown to be safe and effective. The sticking point is how this should happen. And despite a newfound willingness to engage with traditional medicines, Sahpra’s evaluation unit will face practical difficulties in evaluating African traditional medicines — including the lack of written records.
In China, some medical scripts date back centuries, says medical botanist Makunga. “They formalised their own traditional medicines: x amount of this plant, x amount of that plant, x amount of that plant is good for treating disease y,” she said. South Africa’s traditional medicine system — in which dosages are based on individual handfuls and plants may be included because in a dream ancestors told a traditional healer, or an inyanga, to add them — is playing catch up with these more formalised systems.
Meanwhile, disagreement over just how traditional remedies ought to be scrutinised under Western protocols has already surfaced. In September, a regional expert committee on traditional medicine, set up by the WHO, the Africa Centre for Disease Control and Prevention, and the African Union Commission for Social Affairs, endorsed protocols for traditional medicine clinical trials, although the traditional medicine regional adviser for WHO Africa, Ossy Kasilo, told Undark in an email that the protocols were currently being finalised. The guidelines, Kasilo wrote, include a “standard protocol for a multi-centre, randomised, double-blind clinical trial to evaluate the safety and efficacy of herbal medicine compared to the standard of care for the treatment of hospitalised patients with mild to moderate cases” of COVID-19.
In standard clinical trials, after researchers show that their drug is safe in animals, there are four phases. The first includes a small number of healthy people to test for safety and dosage over a few months; in the second, up to several hundred people with the health condition being treated are given the drug for up to two years to gauge efficacy and side effects. The third phase involves giving the drug to between 300 and 3 000 people who have the disease, and can last for a few years, while the fourth phase continues once the drug has been made available to the public. Pharmaceutical companies have to jump through these hoops, says Venter, so other industries, such as supplements and traditional medicines, should have to as well. “The important thing is that the traditional medicine industry — and it is an industry — doesn’t get a free ride,” he said. “It has to subscribe to the same scientific methodologies.”
Not everyone feels that this elaborate and painstaking system is necessary for traditional medicines. While the medicines need to be subjected to scientific rigour, they should not be treated as new chemical entities since they have been in use for centuries, argues Motlalepula Matsabisa, a pharmacologist at the University of the Free State in South Africa who chairs the WHO expert committee. The duration of phases one through three should be shorter and should include the minimum number of people, he says, and phase four should not be necessary since the therapies have already been subject to long-term use.
“People want to know: One, it will not kill me and, two, it will relieve my health problems,” said Matsabisa. He later added: “There is science in African traditional medicines, and let’s prove the science through the methods everyone believes in and understands.”
Others go even further, suggesting no version of a modern clinical trial is appropriate. The Traditional Healers’ Organisation, a voluntary national nonprofit headquartered in Johannesburg, is advocating for self-regulation, rather than the imposition of an external value system. The group’s perspective is that only healers should be able to evaluate traditional medicines and practices, says Maseko, who is also a spokesperson for the organisation. “We can’t be Western medicine,” she added. “And we can’t aspire to be.”
Venter calls self-regulation a shocking idea. “Ask them,” he said, “how they would feel if the pharmaceutical industry self-regulated.”
For many experts, COVID-19 is a stark reminder that humanity is continuously confronted with new diseases. Traditional healers adapt their medicines to this changing world; their formulations and applications have changed as new diseases become more prevalent and others disappear, and they are also used in conjunction with Western drugs — something that did not occur in past centuries.
Indigenous knowledge evolves too, says Makunga. As an example, she relates the story of what happened when she accompanied a healer on a walk in the Eastern Cape province. In the forest, the flowers of Bulbine plants stand out like tiny yellow stars. Traditionally, people have used the plant to treat a range of ailments — from cracked lips to parasitic worms — but Makunga was surprised to be told it was also good for erectile dysfunction.
“This one is really potent,” Makunga recalls the healer saying. “We give it to guys and it makes you come on.” Bulbine plants were particularly important for men who were “full of sugar,” the healer told her, in isiXhosa, the local language. An inability to get or maintain an erection is common among men with diabetes. Diabetes prevalence has more than doubled in the last two decades, with 4.5-million people in the country suffering from the condition. “Twenty-five years ago, this was not something I was treating all the time,” Makunga remembers the healer saying.
Still, there is no peer-reviewed scientific evidence that the plants are an effective treatment for erectile dysfunction in humans, nor has there been any examination of how these plants are used in traditional healing, in what dose, and in conjunction with what other plants. Indeed, the slippery nature of traditional medicine and the context in which it exists presents many challenges for anyone hoping to evaluate its safety and efficacy.
Few studies have been done, for example, on how traditional medicines interact with pharmaceuticals — even though millions of South Africans likely use both on a regular basis. Makunga gives the example of pregnant women who are rushed to hospital. Sometimes they drink a traditional tonic to induce labor, but the contractions become “too intense,” Makunga said. “In the hospital, the doctors didn’t know what they’ve taken.”
Despite these risks, traditional healers often have justified concerns that outsiders will steal knowledge about plants for commercial use without recognising the community from which the knowledge originates. They can point to Hoodia gordonii, a succulent that rises out of the deserts of southern African like fat thorny fingers, as one example. For millennia, hunter-gatherers in the region — in particular, the San people — have chewed its watery flesh to suppress their thirst and appetites on long hunts.
South Africa’s Council for Scientific and Industrial Research (CSIR), tipped off by ethnographic reports of the plant’s use, began investigating the plant in 1963. By the mid-1990s, they had isolated its active pharmaceutical ingredient, P57, in the hopes of developing an appetite suppressant and, without the knowledge of the San, were granted an international patent for the ingredient. In 1998, CSIR entered into a licensing agreement with UK-based company Phytopharm. Following international attention and accusations of biopiracy, the CSIR entered into a benefit sharing agreement with the San people in 2003. In 2010, Phytopharm returned all development and commercialization rights to the CSIR.
Despite the furor around H. gordonii’s appropriation, to date no blockbuster weight-loss drugs have emerged from it and in trials there were a number of side effects, although the plant alone is still widely used. “There is a lot of mistrust of scientists, the belief that scientists steal the information and then make a lot of money,” said Vinesh Maharaj, a plant chemist at the University of Pretoria who was at the CSIR when it brokered the H. gordonii benefit-sharing agreement. Based on how little progress has been made in identifying novel drugs in traditional medicines, the idea that scientists are making money “isn’t true,” he said.
Still, scientists do sometimes publish traditional healers’ knowledge in academic papers without consent, and the history of traditional knowledge theft looms large for many traditional practitioners. Maseko pointed by way of example to the highly-protected, proprietary formula for Coca-Cola. “That’s the thing that makes it Coca Cola,” she said. “If we expose our secrets to the vultures, healing is gone.”
There are other reasons for secrecy. Chabalala, for example, would not reveal which herbs, aside from A. afra and cannabis, that the government is investigating to treat COVID-19. “The minute we say we’re working on it, everyone will hit the forest to unsustainably start harvesting them,” he said. “People will start harvesting them and preparing them not in the way healers use them. People will start researching without benefit sharing and thinking of the wisdom keepers.”
On the streets of Johannesburg and on its outskirts, there are still people claiming to sell A. afra, he said. But they are not healers and there is no certainty that they are actually what they say. Patients could die, Chabalala warns. “Then people will say, ‘You see’,” that’s what happens when you take traditional medicines.’”
Even advocates for greater scientific scrutiny of traditional remedies say that outsiders need to understand the complex system of healing of which they are only a part. Healers are not only doctors, but also counselors and spiritual guides, Makunga noted. “There is an incredible amount of power in somebody just going to a healer, before you’ve started to give a herbal remedy,” she said.
“You would describe a feeling,” she added, “and they start burning imphepho” — a musky sweet Indigenous herb that is used to commune with spirits — “bringing the ancestors, speaking to parts of our feelings aside from the physical.”
But as both a scientist who investigates medicinal plants and as someone who understands their spiritual significance, she says she knows the value of evidence. When someone tells her they use a plant to treat a specific illness, she says she wants to see the research showing that “it works 99.9 percent of the time.”
The statistics are necessary, she said, “because that is my training and line of thinking.”
Sarah Wild is a freelance science journalist based in Johannesburg, South Africa.