Wall Street Journal - July 19, 2001
Mark Schoofs, Staff Reporter of The Wall Street Journal

DAR ES SALAAM, Tanzania -- A pair of South Africans whose attempts to test an experimental AIDS drug caused an uproar in 1997 have quietly tested the compound on humans here with the help of the Tanzanian police and military.

The experimental drug, Virodene P058, is purified from an industrial solvent known as dimethylformamide, or DMF. To its supporters, including Thabo Mbeki, now president of South Africa, Virodene is a potential AIDS wonder drug. To its critics, it is modern-day snake oil that could conceivably make AIDS worse.

Virodene has apparently never been tested against AIDS in animals and is vehemently opposed by many mainstream AIDS scientists. Even so, its developer, medical technician Michelle Olga Patricia Visser, and her former husband, businessman Jacques Siegfried "Zigi" Visser, have organized three human trials of Virodene in three separate countries, either going around the usual public-health regulatory channels or, in one case, operating where regulatory approval wasn't required.

In a continent decimated by AIDS and desperate for a cure, the story of Virodene shows how even an experimental drug with little scientific backing can win adherents. It also spotlights some of the theories about AIDS that are circulating in Africa. For example, Mr. Visser said in an interview that he considers proven "antiretroviral" AIDS drugs too toxic. He also doubts whether HIV causes AIDS and even whether the disease is transmitted through sex.

President Mbeki has also questioned whether standard AIDS drugs are too toxic and whether HIV really causes AIDS.

Much about Virodene and the Vissers' latest tests remains unknown. Results of the Tanzanian trial, conducted between September 2000 and March 2001, aren't complete, say the Vissers and study doctors. The Vissers decline to say who owns the private South African company sponsoring the study, Virodene Pharmaceutical Holdings Ltd. They say they are minority owners, and that Mr. Visser runs the day-to-day business. They also won't disclose the source of the $3.5 million to $4 million Mr. Visser says the study has cost, saying backers are concerned about adverse publicity.

Andrew Kitua, director general of Tanzania's National Institute for Medical Research, says the trial didn't receive proper authorization. But the Vissers maintain their trials have been conducted following the highest international ethical, scientific and safety standards. "We've double-dotted every 'i' and double-crossed every 't'," Mr. Visser says.

The history of Virodene began in 1995. Ms. Visser, then a medical technician working at a hospital in Pretoria, had been trying to freeze animal hearts with DMF so that the organs could be thawed and still function. She says she noticed that DMF killed some kinds of bacteria and wondered if it might work against viruses such as HIV.

In the first trial, she and her Pretoria colleagues gave a purified form of DMF, which they called Virodene, to 11 patients with HIV. Ms. Visser says Virodene, which was administered through a patch so that it seeped into the body through the skin, achieved "magnificent results."

Without waiting for their data to be peer-reviewed, Ms. Visser and two Pretoria colleagues appealed directly to the South African cabinet for funding for more tests. Examining data from the trial, South African health authorities said they saw no evidence that Virodene worked. Health professionals opposed to Virodene sparred with prominent political figures such as Mr. Mbeki, then deputy president of South Africa, who backed the Vissers' efforts.

Ultimately, the University of Pretoria reprimanded two of the study doctors for conducting the trial without approval, and South Africa's drug regulatory agency, the Medicines Control Council, blocked further human tests, saying the substance was potentially harmful and there was scant evidence it would work.

The agency also noted a test-tube study published in 1997 in the journal AIDS Research and Human Retroviruses by University of Washington researchers that suggested that DMF could actually inflame HIV.

Even before the controversy faded, however, the Vissers say they began looking for another country where they could test Virodene. Their first stop was England, which doesn't require government regulatory approval for studies conducted in healthy volunteers for the purpose of evaluating a drug's safety. Documents indicate that the Vissers turned to Guy's Drug Research Unit -- now owned by Quintiles Transnational Corp., a large U.S.- based company that runs clinical trials for pharmaceuticals and biotech companies -- to conduct a small trial of Virodene in London on HIV-negative subjects.

Results of that 15-person study, conducted in late 1998 and 1999, haven't been published, but an internal report by Ms. Visser and Leonard Sequeira, the Tanzania study co-investigator, says researchers concluded that one Virodene patch was "generally well-tolerated" by subjects, while two patches applied simultaneously led to stomach pains and liver abnormalities.

The Vissers' next stop was Tanzania. Their team's proposal to conduct human trials was rejected by a key Tanzania health agency, the NIMR, which noted "major methodological problems which need rectification." But, Mr. Visser says, his company had already "contracted with the defense forces to do the trial for us." According to study documents, a South African subsidiary of Quintiles also participated. A spokeswoman for Quintiles declined to comment on any involvement in any Virodene study.

The study was conducted in two locations in Dar Es Salaam -- a military hospital and a medical clinic that is owned by the country's inspector general of police, according to study doctors. Military and police officials either declined to answer questions about the trial or didn't respond to requests for interviews.

The placebo-controlled, double-blind, randomized trial involved 64 HIV-infected patients, according to trial documents and interviews. It was carried out in five stages, beginning with a group of patients who received one patch a week for two weeks and escalating to the final and largest group, which received one patch a week for six weeks. To monitor for side effects, patients were kept in the hospital or clinic for the duration of their experimental treatment, and for two weeks afterward.

Mr. Visser said in an interview that the trial obtained all necessary authorization, pulling from a file approval letters from international, military and private review boards. He also displayed an approval letter written by Aaron Chiduo, who was Tanzania's minister of health at the time. But Dr. Chiduo says he also instructed the company and army officials to get approval from the NIMR, which is assigned by Tanzania's parliament to monitor medical research carried out within the country. The researchers did apply for approval to NIMR, but were turned down.

Mr. Visser says the trial went ahead because Dr. Chiduo's positive letter "basically overruled" NIMR, a contention Dr. Chiduo strongly disputes. Mr. Visser also says the military doesn't need health department approval to run clinical trials, even though many trial subjects were civilians.

In addition to the trial's authorization, the academic credentials of Ms. Visser raise questions. She says she is a full professor and head of the department of New Technologies in Medicine at Modern University in Lisbon, Portugal. But three officials at Modern, including the director of academic services, Maria Joao Junceiro, say no such department exists and that Ms. Visser isn't listed on the faculty. Despite repeated requests, Ms. Visser didn't provide names of people who might be able to verify her position.

The Vissers do have prominent supporters. South Africa's former minister of health, Nkosazana Zuma, backed their efforts to test the drug.

The Vissers also cite Luc Montagnier, whose laboratory discovered the AIDS virus, as a supporter. Dr. Montagnier says he had discussed collaborating with Ms. Visser to test Virodene in animals to see if the compound enhances other immune stimulants, but isn't familiar with the details of the Vissers' claims or involved in their current work.

-- Ogale Idudu and Erik Burns contributed to this story. Write to Mark Schoofs at mark.schoofs@wsj.com2

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