The AIDS Herb

Despite the wishful thinking of millions of South Africans, Sutherlandia frutescens will not likely prevent or cure AIDS. But scientists believe this gangly legume could, nonetheless, turn out to be a winner.

By Robert Koenig in Cape Town. Photos by Paul Weinberg in Durban.

As rain clouds engulf the summit of Table Mountain above him, Bill Folk makes a beeline through the lush Kirstenbosch National Botanical Garden towards a small, nondescript shrub marked Sutherlandia frutescens. Its plain green foliage pales in comparison to the garden's exotic proteas and other flowering plants, but the gangly legume boasts a stunning botanical résumé.

"Sutherlandia could make its way into medical history," says Folk, a professor of biochemistry and senior associate dean for research at the University of Missouri-Columbia School of Medicine. Folk has for years been making the 9,000-mile trek between MU and South Africa to lay the groundwork for the research that could make that history.

"The plant already has a remarkable story, and it has now become the focal point of our international collaboration to scientifically study African traditional medicines used for HIV infection and AIDS," he says.

At the botanical garden, a marker boasts that Sutherlandia "is an old remedy for cancer and is now also used as an immune booster for AIDS patients." That simple claim, accepted in many South African communities, poses a complex challenge for Folk and collaborators who are trying to separate fact from legend. Do the dried leaves of Sutherlandia, sipped as an herbal tea or taken as pills, have an impact on people whose immune systems are being compromised by infection with HIV?

That question and related issues took Folk from his laboratory at the University of Missouri-Columbia's medical school on a working visit this summer to South Africa, where the human immunodeficiency virus, HIV, infects an estimated 5.5 million people, more than any other nation.

Every day nearly 1,000 South Africans die from AIDS-related diseases and a similar number are newly infected. The epidemic, which now affects nearly 20 percent of the adult population, shows few signs of slowing down, despite a recent ramp-up in the government's prevention and treatment programs.

As part of this vigorous, if tardy, intervention campaign, practitioners of modern medicine have brought some of their most potent weapons to bear on HIV, spearheaded by antiretroviral, or ARV, drugs. At the same time, many traditional healers -- who are consulted by a startlingly high number of South Africans -- have been dispensing Sutherlandia as a tonic to slow the wasting associated with the disease. Even though the herb is used by thousands, there has been little clinical research on the safety and effectiveness of Sutherlandia, or, for that matter, on other traditional remedies.

That is about to change. The first scientific clinical trial of Sutherlandia is scheduled to start this fall at Edendale Hospital in the province of KwaZulu-Natal, the epicenter of the nation's HIV/AIDS epidemic. "This is a groundbreaking clinical trial," says Folk, who, along with South African researcher Quinton Johnson, leads the International Center for Indigenous Phytotherapy Studies, or TICIPS, which is responsible for supporting the Sutherlandia trial.

Getting to this stage in the research has been surprisingly difficult. In a nation where every approach to dealing with the HIV epidemic seems to be mired in controversy -- South Africa's president at one point questioned the link between HIV and AIDS, and the health minister has stubbornly advocated nutritional remedies for HIV infection -- merely gaining approval for Sutherlandia trials from the government's Medicines Control Council and other regulatory boards took two years.

To satisfy these agencies' requirements for ensuring safety, researchers first conducted a pilot study involving about two dozen healthy people near Cape Town. The study found that the Sutherlandia pills used by many South Africans had no discernible harmful effects.

With those results in hand, Folk and his colleagues have the green light to conduct the first randomized, placebo-controlled clinical trial of an African traditional medicine in HIV-infected adults. The trial was announced with much fanfare in Durban on August 30 at a news conference that included the head of the Medical Research Council, the provincial Minister of Health, physicians, traditional healers and scientists.

Johnson, a professor at the University of the Western Cape, UWC, heads the university's South African Herbal Science and Medicine Institute. It was a logical site for co-locating TICIPS because of MU's long-standing relationship with UWC. In a conference room at the institute, Johnson and Folk -- sipping Rooibos tea, a South African herbal brew internationally touted for its health benefits -- recounted the history of the cooperative effort that led to the clinical trial.

"In Africa, traditional medicines and healing practices were repressed for years by colonial powers, for they were considered to be witchcraft," says Folk. "Only with the loss of that power has the repression of traditional medicine been lifted."

Africans often use traditional medicines because they have only limited access to Western pharmaceuticals, he adds. In some communities, people are left to self-medicate, acquiring traditional plants and other remedies on their own with only occasional visits to local healers.

"Even people being treated by Western-trained physicians continue to treat themselves with traditional medicines, and in some cases, to see traditional healers," says Folk. "Understanding this will be a huge factor in the sustainability of antiretroviral treatments, which are likely to be affected by the traditional medicines."

After obtaining a planning grant for their studies, the TICIPS group was, in October 2005, awarded one of two major "international research center" grants from the National Institutes of Health's National Center for Complementary and Alternative Medicine. The $4.4 million, four-year grant aims to help TICIPS determine whether traditional medicines are, according to the proposal, "safe and beneficial to the health and wellbeing of the African public using traditional medicines."

The researchers say the funding will also bolster South Africa's research capacity, while helping to preserve "systems of traditional and indigenous knowledge," and the nation's rich biodiversity. Today there are 15 South African researchers involved with TICIPS and an equal number from the United States.

South Africa has a long tradition of healers, from the ancient Bushmen to the powerful Zulu and Xhosa sangomas -- practitioners of herbal medicine and divination who still have great influence in some communities. Unlike traditional medicine in China and India, few of the African remedies have been preserved in writing. What is known has instead been passed down via oral tradition from healer to healer.

Today there are vast traditional medicine markets, called "muthi" markets, in big cities. While some physicians regard forms of traditional healing methods as quackery, there are plenty of precedents supporting the effectiveness of plants used by traditional healers.

A prime example is quinine, an extract of cinchona tree bark that has been used for centuries to treat malaria. Aspirin, the world's most popular pain reliever, was derived at the end of the 19th century from a compound in willow tree bark. More recently, a natural compound called taxol, produced by the Pacific yew, has become an important cancer-fighting drug.

Johnson, whose grandmother was an herbal healer in the Cape Town neighborhood where he spent his childhood, says the use of traditional herbs is not about to disappear in Africa. "Whether or not we conduct clinical trials on these traditional remedies, millions of people will continue to use them," Johnson says. What researchers can do, he adds, is bring scientific evidence to the mix.

When it flowers, Sutherlandia -- known to botanists as Lessertia frutescens -- is an attractive shrub, sprouting scarlet flowers that later bear fruit as inch-long inflated green seed pods that give it the nickname "balloon pea." The plant grows in much of South Africa's Western and Northern Cape provinces, where it is often called the "cancer bush" because residents use it as a tonic to fight weight loss in cancer patients.

The leaves have been used in South Africa as traditional medicines since they were first adopted by the Khoi, San, and Nama peoples. In fact, the traditional Tswana name "phetola" means "it changes" -- implying its effectiveness in treating some conditions. European settlers remarked that the Hottentot tribesmen sipped Sutherlandia teas in the 17th century. It was one of many plants used by African tribes as medicines: Sarcocaulon was taken to stop diarrhea, powdered Berkhya leaves were used to soothe boils, and the wild rosemary plant was prescribed against stomach aches.

"It's clear that Sutherlandia has been used for centuries by traditional healers," says Wendy L. Applequist, assistant curator at the William L. Brown Center for Plant Genetic Resources of the Missouri Botanical Garden in St. Louis, and a partner in the TICIPS effort. The Brown Center is world renowned for its studies of medicinal plants and related topics of ethnobotany, the study of how traditional societies use plants for healing and other purposes.

During a discussion in the garden's research center, Applequist explained that one of her goals in collecting Sutherlandia specimens in South Africa last fall was to determine whether "various populations of this plant are chemically similar."

Gathering a diverse group of samples wasn't easy, as the plants grow in small, widely-scattered populations. Applequist got help from local botanists in the Eastern and Western Cape provinces to find areas where the plants grow. "It was a challenge, but we were able to gather samples from quite a few sites and send them back to labs here and at the UWC," she says.

Another partner in the TICIPS project is the National Center for Natural Products Research at the University of Mississippi, which is studying the composition of chemicals in Sutherlandia. Researchers at the Oxford, Miss., center hope to find a "marker" that is detectable in human blood plasma. That would help confirm that people taking part in a clinical trial are absorbing the plant's ingredients.

"The average plant contains hundreds of chemical compounds, found in suites," says Applequist. "It's a painstaking and expensive process to isolate and characterize those compounds, as well as to find out how they function." She says Sutherlandia contains compounds such as pinitol, which has been shown to benefit some diabetics, and canavanine, an amino-acid analog that can cause problems if taken in high doses.

The South African government estimates that 20,000 tons of medicinal plants are used by at least 27 million South African consumers each year. Included among them are some highly questionable mixtures marketed as HIV/AIDS remedies. One of the more popular is a concoction called Ubhejani, the Zulu word for rhino, which is sold in plastic bottles on the streets of Durban and elsewhere in KwaZulu-Natal.

University of Cape Town economist Nicoli Nattrass, an expert on the impact of the HIV/AIDS epidemic on South Africa, criticizes the government for being lax in its regulation of untested remedies. A Ubhejani proponent, for example, was named recently to the Presidential Task Team on African Traditional Medicines, a group charged with developing a regulatory framework for such remedies. Gareth Morgan, a health expert with the main opposition party, wants to ban Ubhejani and other remedies until they are tested. "An appropriate evaluation system for traditional medicines will be of enormous benefit to South Africans," Morgan says.

The use of traditional remedies is hardly limited to Africa. In the United States, nearly one-fifth of people surveyed used natural products, with the most common being echinacea extract, ginseng, ginko biloba, garlic supplements, glucosamine and St. John's wort. The NIH is supporting research on those and many other natural products.

TICIPS manager Eugene Sickle, an organic chemist at UWC, embraces this focus on the big picture. "We look holistically at traditional medicine," he says, "[while] trying to explain the phytochemistry of the plants that are used." For example, one student is testing a number of over-the-counter Sutherlandia medications, including five tablets and two gels for anti-oxidant activity. While none of the packages claim the herb fights HIV infection, they advertise "immune booster," "anti-oxidant" or "immune modulator" qualities, as well as effectiveness against eczema, acne, psoriasis and shingles.

"We have identified about 100 plants that we would like to look into, but the costs of clinical trials are very high," says Sickle. "So we narrowed down that list to about ten." The first of them to be clinically tested is Sutherlandia.

At the edendale hospital, a giant, red-brick complex in Pietermaritzburg, KwaZulu-Natal, men and women wearing traditional Zulu sangoma gear, including colorful costumes and beaded headdresses, file into lecture rooms to meet with doctors specializing in HIV/AIDS and tuberculosis.

The healers are part of a program organized by the University of KwaZulu-Natal's Nelson Mandela Medical School, partially funded by U.S. dollars, to try to bridge the wide gap between African traditional and Western medicines. More specifically, it seeks to encourage the traditional healers to refer people with the symptoms of HIV/AIDS to specialists at the Edendale clinics.

Edendale is one of the major treatment facilities for HIV/AIDS patients in KwaZulu-Natal. About 60 percent of the hospital's patients, including 44 percent of pregnant women, are HIV-positive, says Edendale's chief of medicine Doug Wilson, the South African physician who is leading the Sutherlandia trial together with clinical psychologist Kathy Goggin of the University of Missouri-Kansas City.

"This is the first time a traditional medicine has undergone such a clinical trial in Africa," Wilson says.

The first phase, lasting about six months, will determine safety and whether there are any side effects; the second phase, lasting at least 48 more weeks, will help researchers determine whether Sutherlandia has any measurable impact on the sample of 124 HIV-infected people who take the herbal remedy.

Cardiologist Anthony Mbewu, president of South Africa's Medical Research Council, says such trials are crucial in a nation where an estimated 80 percent of the population use traditional medicines. He cites the TICIPS research as among several projects that are examining "potential immune-boosters, testing the safety and toxicity of some South African plants." At the same time, he says South Africa is negotiating formal collaboration with China and India to study the use of traditional medicines in connection with HIV/AIDS.

UWC's Johnson says there are an estimated 200,000 traditional healers in South Africa, but only about 20,000 medical doctors. "There is currently no bridge between scientists and sangomas," he says. One step toward creating such a bridge is a pending South African law for registering traditional healers. Johnson says the healers' council requested the new law "to help distinguish between true traditional healers and the charlatans who are simply trying to make a fast buck."

In Zulu communities, a typical healer will see about 2,000 patients a year, according to Nceba Gqaleni, a professor at the University of KwaZulu-Natal's medical school and the point man for TICIPS work with traditional Zulu healers. He estimates that almost all healers are able to identify the symptoms of HIV/AIDS infection.

Gqaleni has been "essential to this project," Folk says. "Without him, we would not have had the cooperation and support of the traditional healers."

Many traditional healers have argued for wider use of Sutherlandia to help treat HIV-infected people, including South Africa's highest-ranking healer, Credo Mutwa, author of the best-selling book Indaba, My Children and a leader of the nation's main organization of traditional healers. "I don't claim this is the cure, but what it does to people is amazing," Mutwa said during a 2001 interview.

Reports of such tonic and immune-boosting qualities are the chief reason Sutherlandia is the first traditional medicine to be tested clinically. But another important question for modern medicine -- an issue likely to be addressed in future studies -- is whether the compounds in Sutherlandia influence, positively or negatively, the cocktail of drugs that a quarter million South Africans take as antiretroviral therapy against HIV infection.

"People being treated by Western-trained physicians often continue to treat themselves with traditional medicines," says Folk. "We need to find out whether this affects the success of antiretroviral treatments." Clinician Wilson agrees that, even though traditional remedies are widely used, "it is rare for people to know their potential side effects. And it is extremely important that we find out."

Now that the Sutherlandia clinical trials are on track in KwaZulu-Natal, Folk is working to expand his studies of traditional healing and HIV/AIDS to other parts of Africa. In September, he traveled to Kenya to plan "a small pilot study to document traditional healing practices used by the HIV-infected public." He hopes to set up similar studies in Zambia and Uganda.

"I have the interest and support of several of the largest antiretroviral treatment programs in Africa for such efforts," Folk says, "as they recognize their care is mixed with use of traditional medicines, about which so little is known."