Since May, 32 patients with malaria at Mumbai’s King Edward Memorial (KEM) Hospital have been directed to its Ayurveda research cell. There, a team of 12 doctors is conducting trials of a formulation and its action against malarial parasites.
If a patient agrees to participate, she will be checked into the hospital, fed and looked after for three days, and placed in one of two groups. In addition to chloroquine and primaquine, one group will get a paste of parijat leaves thrice a day, to be washed down with a glass of water. The other group gets a dummy paste.
Doctors draw patients’ blood daily to measure liver and kidney enzymes and to do a complete blood count—two tests that track the spread of the parasite.
“We don’t have all the numbers yet to analyse the results, but it seems very encouraging,” says Nutan Nabar, an Indian Council of Medical Research (ICMR) fellow at the Kasturba Health Society (KHS), who is leading the trial. “It is reducing nausea and inflammation, but we have to wait for all the results to come in.”
This is one of India’s first few Ayurvedic clinical trials done at a recognized institution, and the journey has not been easy.
Indeed, the story of the trial is a marvellous case study of why Ayurvedic research has stagnated in India. Due to the government’s inability to draft a cohesive policy for Ayurveda, research is stuck in a format meant for modern medicine, with researchers who have little training and rigour. Meanwhile, policymakers don’t have the imagination to consider alternative ways to test drugs.
Experts say that until a policy is drafted and a research model settled upon, nothing will progress. Only then can the system address its other problems—lack of infrastructure, trained manpower, and data collection and follow-through.
The malaria trial began several years ago, says Ashok Vaidya, the principal investigator and research director at KHS, who trained in clinical trials at Yale University and pioneered reverse pharmacology in Ayurvedic research. (In reverse pharmacology, scientists examine drugs that have been used for several decades, to study their activity using modern criteria and figure out which molecule of the plant acts on a disease.)
Vaidya’s interest in pharmacology began as a child. “I saw my parents giving Ramban tablets to hundreds of malaria patients and mailing them to thousands. My great-grandfather, who was a vaidya (healer), started it. So the family that I grew up in unfortunately also depended upon malaria continuing. As I child I used to wonder: ‘Why can malaria not be eradicated?’ So it was a deep motivation that if something can be done to fix this, it would be worthwhile.”
Alternative remedy: A lab at Kasturba Health Society
When he got an opportunity 15 years ago, Vaidya jumped at the chance to study the impact of the parijat plant against malaria, in collaboration with D.S. Antarkar, a famous vaidya. “Antarkarji, in his tradition, was using parijat, and in my tradition, my great-grandfather had mentioned in his notes that parijat has anti-malarial activity.”
Together, they performed a “clinical screening, where Antarkarji gave the Ayurvedic treatment and I observed responses using modern criteria,” Vaidya says. “That’s how the idea of reverse pharmacology was born.”
They got results, and so a team of four doctors—P.S. Tathed, Sirish Karnik, Chayya Godse and Akhil Vaidya—investigated further.
“We worked against great odds, and we observed that the parasite disappeared with the paste of leaves,” Ashok Vaidya says. “We also measured the DNA of the parasite in the blood by collecting blood spots, which were taken to Philadelphia for analysis. The results were so astonishing that people sat up and took notice. For the first time they felt: Maybe there is something to this Ayurveda.”
“The problem is that we don’t ask the simple question: If our great vaidyas have all written the same thing, why should they all be bluffing?” Vaidya argues. “If Antarkar has found one answer for malaria, if Mayaram Vaidya has also found it, if Vaidya Desai has also found it, if somebody in the north has also found it, to me that is also consensual validity. The Western statistical model is not the only model, it is not the only path.”
Thus, when the KHS-ICMR advancement centre was formed in 2007, Vaidya’s malaria trial became one of the first projects to get off the ground. “We had data of 140 patients, and we got permission from the Inter-System Biomedics Ethics Committee (ISBEC) to do more research,” Nabar says. “We wanted to do this at the most respectable research centres, and since KEM has an Ayurveda research cell, it was a natural choice.”
Recounting the struggles of the last two years, Nabar says: “After securing the permission from ISBEC...the team approached the ethics committee at the hospital for permission to begin the trial.” But there was no Ayurvedic expert on the board, and its understanding of reverse pharmacology was dim.
“They didn’t want to let us do it until we provided the safety data. The FDA (the US Food and Drug Administration) rules say that if a formulation has been in the market for 10 years, then it is safe,” Nabar says. “Well, it was in the market as a paste, but because we were going to administer it (as) tablets, the committee ruled that it was a different formulation and all safety tests must be done.”
The team thus spent months on toxicity studies. When they were submitted, the doctors were told that withholding chloroquine (the regular drug for malaria patients) was unethical. Hence the two groups, where one received chloroquine and parijat paste and the other chloroquine and a dummy drug.
Next came a demand for stability studies. “The tablets were ready and Ashok Vaidya, who was principal investigator, was very disappointed,” Nabar says. “He told us: ‘Do whatever they want. Just get it off the ground.’” We finally hammered out the protocol in March 2008. After which, the committee asked us: ‘Do you have insurance for the study? If any problem arises, then insurance is a must for every patient.’” Another two months elapsed. “All this,” Nabar groans, “for a formulation that has been used for 2,000 years to treat malaria.”
The trial’s researchers don’t blame the ethics panel; instead, they say, it is the fault of a system that can’t recognize that Ayurvedic research needs a different model.
Last month, in another demonstration of how little officials understand the needs of traditional medicine, the government issued a new set of clinical research guidelines for Ayurveda. They were borrowed, almost word for word, from ICMR’s guidelines for modern medicine.
D.B.A. Narayana, one of India’s most renowned Ayurvedic scientists, who has introduced over 50 herbs into the Indian herbal pharmacopoeia, says: “We’ve adopted a drug development model and wanted to fit Ayurveda into it. We took oranges and wanted to measure them with apples. There were some successes. But in a number of cases it failed. Our approach was totally reductionist one where we took science—biology, physics, chemistry—into a holistic approach and demanded that it should answer which part of the body, cell, gene it acted on. How can you do that?”
Louis Lasagna, an expert of clinical pharmacology at John Hopkins University and a pioneer of double-blind trials, agrees that such controlled trials can’t be applied to traditional medicine, where “experiential documentation by many” is a very important part of evidence that it works.
Protection of knowledge
In the shadow of a powerful pharma lobby, pharmacists aren’t surprised that Ayurveda research has languished. “The industry is fighting for things like data exclusivity, patents, intellectual property rights (IPR)... What is the IPR protection for Ayurveda? Zero,” Narayana says. “And since you don’t have any protection of any research that you do, the industry doesn’t want to do any research.”
In a hypothetical case that Narayana describes, a firm may invest crores in a clinical trial of a particular Ayurvedic product and formulate a drug. “The next day, 50 other folks are using the same data to create the same formulation,” Narayana says. “Why would anybody invest? Research in Ayurveda is going down day by day because of no protection for traditional knowledge and over-protection for others.”
Even if someone makes the effort, Narayana explains, there is no assurance of reward. “Raghunath Mashelkar (a renowned vaidya) did a partnership project in which Ayurvedic leads were taken for arthritis, diabetes and hepatitis,” he says. “The leads were put through the complete validated drug development mode, including Ayurvedic testing. It worked. But there were no takers for their products. The modern doctors...turned around and said: ‘I’m so sorry but I cannot prescribe this medicine because I’ll be called a quack.’ The Ayurvedic vaidyas said: ‘We will write the preparation from the sacred texts only. Why should we prescribe your formulation?’”
And so, after a long struggle, the lone Ayurvedic researcher who arrives in the market can still end up holding the baby on the sidewalk because there is no policy to put these shiny-new, data-driven drugs into the high street.