Today, we have for our readers, a guest post by Priyanka Pulla, a freelance journalist, on the difficulties in developing modern drugs from Ayurveda. A couple of weeks ago, Priyanka had written this excellent piece, titled “Ayurveda: Hoax or Science?” which featured as the cover story on Open magazine. After reading the story, I invited Priyanka to write us a guest post on the Ayurvedic drug industry and she has indulged us with the following post on the issues faced in developing modern drugs from Ayurveda.
THE COMPLEX PROBLEM OF DEVELOPING MODERN DRUGS FROM AYURVEDA
By, Priyanka Pulla
In My Feb 2013 article in Open Magazine (read the complete story here), I researched why so few modern drugs had emerged from Ayurveda. For the many claims and research into Ayurvedic medicines that we come across, only a handful of modern drugs such as Reserpine have emerged from Ayurvedic leads. Reserpine, though, is a single molecule isolated from an Ayurvedic herb called Sarpagandha. Herbs in their natural form, such as Sarpagandha, Ashwagandha and Brahmi extracts, have no acceptance in modern medicine at all. They cannot be prescribed by modern-medicine practitioners as a cure for any disease, and can only be sold as dietary supplements. This means modern medicine does not accept the claims of Ayurveda. Why is this so? My article cited three reasons:
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It is very tough to develop modern drugs from herbs. Herbs are complex mixtures of compounds and most modern drugs are single, pure compounds. Secondly, the quality of herbs varies from place to place and season to season. Finding the herb with the right potency is itself a major challenge. Then, one has to find the molecule in the herb that is causing the desired effect (in Sarpagandha, it was Reserpine). This is also a big challenge.
The odds have been stacked against traditional medicine because modern medicine took time to wrap its head around the mechanism of action of herbs. For a long time, the USFDA (United States Food and Drug Administration) required herbal drugs to undergo the same tests that synthetic drugs undergo to enter the markets. This means the active ingredient had to be identified for a herbal medicine to become a modern drug. This is difficult because many Ayurvedic drugs contain multiple active ingredients, and which one really works is often not established for years. Also, herbal mixtures vary from batch to batch during production—this presents a problem. How do you ensure that each patient receives a drug of the same potency and efficacy? Today, the USFDA has created new guidelines for herbal medicines. They need to provide lesser safety data, given their long history of safe use, and they need not establish the active ingredient. All this helps herbal drugs immensely.
In my story, I used the USFDA as a proxy for the modern medical stance. This is arguable, because countries such as Canada take a more lenient view of herbs, and yet, the FDA’s stance is fairly widespread. A number of Indian scientists I spoke to, such as Ram Vishwakarma of IIIM, talk of FDA requirements as a good standard to follow. They think Ayurvedic drugs should make an attempt to adhere to them. India, in comparison, has been too lenient towards the herbal-drug sector, not requiring any clinical trials for it. So, I couldn’t obviously use the Indian regulatory stance as a proxy for scientific acceptance.
India itself hasn’t done much to encourage herbal-drug development. Firstly, there are very few regulations for this sector, and Ayurvedic drugs don’t need to provide much scientific validation. Secondly, given the high failure rate in drug development, bodies such as India’s Department of Ayush ought to have encouraged extremely large-scale clinical trials and testing, as China has.
Instead, our herbal-drug development initiatives have been small and beset with duplication. Too many institutions are repeating the same work—the Department of Science and Technology, the Department of Biotechnology and so forth. This is partly why there are so many studies out there on Ayurveda, but put together—these don’t add up as conclusive proof of efficacy of the drug. The way to develop a drug is to pick up a single herb that shows activity and take it through the entire 10-15-year cycle of drug development. Instead people are doing disconnected research, which is widespread, but doesn’t help in validating Ayurvedic medicine.
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According to Chittaranjan Andrade, who heads the department of psychopharmacology at Bangalore’s National Institute of Mental Health and Neurosciences, the only thing that matters at the end of the day is clinical trials. He says many herbal drugs seem to be very active in animal studies, but fail in humans. Andrade, who himself has carried out clinical trials on herbs with claimed central nervous system (CNS )effects, such as Ashwagandha, Brahmi and Shankhapushpi (which are prescribed for indications such as anxiety and poor memory), says no definitive clinical trial exists for any of these herbs.
Plus, some of the research out there is very unscientific. I had contacted the CCRAS, which is India’s apex body to promote Ayurveda, asking if the many trials published on their website, claiming miracle cures, were indeed placebo-controlled trials. Nobody responded. Later, many scientists told me off the record that those trials were of very poor quality. If this is the state of India’s apex Ayurveda-promoting body, how can we hope for better from the private sector?
CAN NON-DRUG INTERVENTIONS BE TESTED THROUGH PLACEBO-CONTROLLED CLINICAL TRIALS?
Having said all this—there were a few other points beyond the scope of the Open story that I’d like to bring up in this blog post. The Open story mainly discusses the subject of drugs, but Ayurveda is an entire system of medicine that entails lifestyle changes and non-drug interventions such as Panchakarma—a set of practices including purgation, massages, sweating, enemas etc.
One thing some of the scientists I spoke to wanted me to highlight was that Ayurveda should not be looked as a source of drugs alone. “Ayurveda is not just a ‘drug bank’…it has some very interesting concepts totally foreign to modern science,” says Venil Sumantran, adjunct professor in the department of Biotechnology at IIT Madras. These scientists say Ayurveda must be looked at for its method of diagnoses, its etiology, the way it views illnesses as holistic, and concepts such as the Tridosha classification.
This is an area that is as poorly researched as Ayurvedic drugs. Moreover, the gold-standard of clinical research—the double blinded, randomized, placebo-controlled clinical trial—probably doesn’t apply here. After all, how do you control a trial on Panchakarma for placebo? The patient knows exactly what treatment she is receiving, so you cannot ‘blind’ the trial either.
Further, Ayurvedic herbs are often administered along with such interventions. So the next question is—is it right to test Ayurvedic herbs in isolation?
The answer is yes. After all, Ayurvedic herbs do make specific claims about curing diseases, don’t they? If a herb claims to reduce anxiety in a patient, it should work in isolation, minus the lifestyle changes accompanying it. If it doesn’t, it must not be sold over-the counter, in isolation, which many Ayurvedic herbs are.
Secondly, we need to know if modern medicine has already created drugs better than these herbs. That needs to be tested, given how long it has been since the ancient Ayurvedic texts were written.
A sentence from a 1994 research paper by ethnobotanists Paul Alan Wilcox and Michael Balick about traditional medicine systems puts this in perspective. As ethnobotanists, Wilcock and Balick travel around the world, staying with ancient tribes and exploring their systems of medicine in an attempt to develop modern drugs from them. Talking about their investigations into herbs used by Samoan healers, Wilcox and Balick say, “We should note, however, that few of the compounds exhibiting activity in laboratory tests will become new drugs. Some will turn out identical to, or less potent than existing agents; others will prove too toxic for commercial use.”
This is really the key. The herbs described in Ayurveda may be potent—no one is denying that. But are they as potent as modern drugs used for the same indications? At the dosage levels they are potent enough, are they non-toxic?
The argument that all natural herbs have no side-effects is incorrect. Look at Veregen, for example, the first herbal treatment approved as a drug by the USFDA. It contains an extract of green tea, and like any other modern-drug, could have undesirable side effects such as redness, swelling, sores or blisters, burning, itching, pain (from the firm’s website). St John’s Wort reduces the effects of several drugs, while compounding the effects of certain antidepressants such as SSRIs. Therefore, it is important to study the herb’s interactions with modern drugs too.
SHOULD HERBAL DRUGS BE SUBJECT TO DIFFERENT CLINICAL-TRIAL REQUIREMENTS?
There is another viewpoint among proponents of Ayurveda that I must highlight. This came from Dr Ashok Vaidya, who heads research at the Indian Council of Medical Research’s Centre for Reverse Pharmacology. He believes Ayurvedic herbs should not need to go through clinical trials the way modern medicines do. Why should an Ayurvedic drug firm have to spend $1bn going through the entire clinical-trial cycle when the safety of the drug is already proven, he asks?
He may have a point there.
After all, the FDA did publish guidelines for herbal drugs only in 2004, which made it easier to develop herbal medicines. Before this, not a single herbal medicine had been approved as a modern drug. The FDA did eventually realize that many of these medicines come with hundreds of years of safety data and so, maybe the process of herbal drug development could indeed be simplified further. Vaidya says certain clinical-trial phases relating to safety can be skipped. Clearly, Vaidya’s views are debatable at this point, and unless a regulatory body takes the call, journalists like me can’t really tell.
OIL AND WATER
Finally, another big problem with herbal-drug development is that, by and large, modern-medicine practitioners and Ayurvedic doctors don’t really talk to each other. This was the impression I received from several scientists. Some of the research personnel at IIIM Jammu spoke about how the Golden Triangle project failed because Ayurvedic doctors and scientists couldn’t reach common ground on the quality of herbal preparations to be tested.
This problem was also highlighted by Dr Bhushan Patwardhan, who headed several of India’s herbal-drug development programs under the National Millennium India Technology Leadership Initiative or NMITLI (see Open story). Even though no drug has emerged from this program, Patwardhan calls NMITLI a success because, for the first time, Ayurvedic doctors and modern scientists began talking with each other. According to him “Projects such as NMITLI should not be looked at from the product point of view. Its (NMITLI’s) most important deliverable was people. It was a great human-resource effort where scientists from the two sectors began talking to, working with and respecting each other. Earlier, they were like oil and water. NMITLI broke this wall; this was its most important achievement.”
Informative post Prashant. I wish the officials at the IPO and higher up in the Ministry would read this and understand how difficult and complex it is to make a new herbal composition or a drug from Ayurvedic sources. The recent guidelines on TK related applications contain illustrations which conclude that it is toy’s play and therefore, cannot be held novel or inventive. Hence not patentable. Thus, identifying a source, processing it, identifying a potential drug candidate from it, extracting and purifying the same and then formulating it in an administrable dosage is all child’s play according to the said guidelines.
So much for applying sense to nonsense!
Anon!
Excellent post MR. PRASHANT, the challenge of modernizing drug development using Ayurveda is indeed a complex one. I appreciate the efforts of the Author in putting the facts from the guest post. Ayurveda, an ancient system of medicine that originated in India, offers a wealth of traditional knowledge about herbal remedies and holistic health practices. However, integrating this traditional wisdom into the modern drug development process involves several hurdles that need to be carefully navigated.
Standardization and Quality Control: Ayurveda relies heavily on complex herbal formulations that have been developed over centuries. The variability in the composition of these herbal mixtures due to factors like geographical location, harvesting time, and processing techniques poses a significant challenge. In modern drug development, ensuring consistent and reproducible quality is crucial for both safety and efficacy.
Scientific Validation: While Ayurvedic texts provide detailed descriptions of herbs and their effects, modern drug development requires rigorous scientific validation through clinical trials. Adapting these traditional formulations to meet modern standards of evidence-based medicine often involves isolating active compounds, determining optimal dosages, and conducting clinical trials to demonstrate efficacy and safety.
Intellectual Property and Patenting: Traditional knowledge, including Ayurvedic formulations, has been passed down through generations. However, reconciling this collective heritage with the intellectual property rights required for modern drug development can be challenging. Preventing biopiracy while incentivizing research and development is a delicate balance that needs to be struck.
Regulatory Compliance: Modern drug development is subject to stringent regulatory requirements that ensure safety and efficacy. Adapting Ayurvedic formulations to meet these standards might involve significant changes in manufacturing processes, dosages, and even the exclusion of certain ingredients. Navigating these regulations without compromising the essence of the traditional remedy is a complex task.
Cultural and Ethical Considerations: Ayurveda is deeply rooted in cultural and ethical contexts. Integrating these traditions into the modern drug development paradigm requires sensitivity to these factors. Collaboration with local communities and practitioners is essential to ensure that the development process is respectful and benefits all stakeholders.
Combination Therapies: Ayurvedic treatments often involve holistic approaches that combine herbs, diet, lifestyle modifications, and therapies. Adapting such multifaceted approaches into the modern drug development model, which typically focuses on isolated compounds, poses a challenge. Finding ways to assess the efficacy of these holistic regimens using modern scientific methods is a complex endeavor.
Global Acceptance and Recognition: Ayurveda is a part of India’s rich cultural heritage, but gaining global acceptance for its principles and treatments requires demonstrating its effectiveness in a way that resonates with international scientific communities. Bridging the gap between traditional knowledge and modern scientific understanding is essential for Ayurveda to be recognized on a global scale.
Addressing these challenges requires a collaborative effort involving scientists, researchers, practitioners, policymakers, and communities. A balance between preserving the integrity of traditional knowledge and integrating it with modern drug development practices must be achieved to unlock the potential of Ayurveda in providing safe and effective treatments for modern healthcare needs.