by Geewananda Gunawardana, Ph.D.
(Part I of this article appeared in The Island of 15 Jan., 2025)
The magic bullet theory was so convincing that it was presumed that all medicinal plants would have a single chemical compound that is responsible for its therapeutic property. This ensued a massive effort to isolate and identify the active chemical compounds not only from medicinal plants, but from all living organisms. Not only the pharmaceutical companies but the universities got involved in this effort earnestly as it offered the promise of curing all diseases. Thousands of hither to unknown compounds were identified, and some, albeit an exceedingly small number of them, were found to be useful in clinical use.
This isolation and identification process were done using bioassays: a pathogenic agent or the cells from a disease tissue, cancer for example, are grown in a test tube and the compound is added to see if it can kill the organism or the cells. As these tests are done in glass vessels, they were referred to as in vitro tests in Latin. A large majority of the compounds had in vitro activity. In academic settings, these findings lead to numerous publications, theses, and patents. But according to the rules enacted in 1962, that is not enough to be called the compound a drug. Its safety and efficacy must be demonstrated beyond doubt.
This is an arduous process including many steps: A) Preclinical studies often involve the demonstration of the activity in animal models of the disease. B) Phase I studies involve testing a crude formulation of the compound in healthy volunteers to assess the harmful effects and identify a suitable dose. C) Phase II studies are conducted with a well-designed formulation on a limited number of patients who qualify to receive experimental therapy. D) Phase III studies are done with a large number of patients to confirm the efficacy and safety in a statistically significant manner. The average cost of this process is $ 1.3 billion and takes an average of 12 years. The overall success rate in clinical trials is about 10%.
The overwhelming majority of the compounds from medicinal plants failed in preclinical studies. Not only did the pharmaceutical industry give up medicinal plant research as a result, but it also left a lasting negative impression in the research community: herbal remedies are nothing but deceptive marketing, health care fraud, or scams. The industry turned to synthetic compounds and biologics, the bioengineered proteins, and produced lifesaving drugs, but at a cost.
Nature of science
The nature of science is that it continues to evolve as more information becomes available. The advances in biology made it clear that the magic bullet theory was based on incorrect information. Chronic diseases have multiple causes, and in real life, the drugs designed to a specific target act on multiple targets. Thus, the term Polypharmacology came into use. It is common to use more than one drug in some treatment regimens. It will take some time before the industry changes direction, but the regulatory agencies saw the truth: they made allowance for plant preparations of defined composition to enter clinical trials.
Researchers who were confident about the utility of some of the centuries old recipes argued that their efficacy is due to polypharmacology, meaning there is more than one compound responsible for their medicinal properties. Based on this justification, instead of pure compounds, many preparations traditionally used for chronic diseases that had no standard therapies were taken through clinical trials. While some efficacy was seen, they were not statistically significant for regulatory approval. In such cases, sponsors of the trials tend to claim that the preparations were clinically tested, even though the regulatory approval was not received. What is going on?
Now we understand the problem, and there are two of them: one relating the medicinal preparation, and the other with the patients. Research has shown that there are multiple compounds responsible for their activity. In addition, there are other compounds that modulate the absorption from the gut and distribution into central nervous system, for example. There are some others that modulate the metabolism, and as a result any toxicity. Unfortunately, in most cases there is no information on these auxiliary compounds needed for efficacy; and most researchers focus only on the active compounds identified in previous studies. And the plant preparations are standardised for such compounds. Plant materials are highly variable; age, season, location, harvesting and storage can change the composition.
Chronic diseases
On the patient’s side, most chronic diseases are not homogeneous, that is, they have multiple causes, and they also can stay asymptomatic for a long time, sometimes decades. As a result, they may not respond to the preparation being tested. A third factor is the placebo effect. For statistical analyses, clinical trials are required to have a patient population that does not receive the drug being tested. They receive a pill that does not have the drug, a placebo, but the mere thought that they are being treated makes them get better. The placebo effect can be extremely high, and it often masks the benefits of the drug.
The good news is that now technology exists to overcome all these shortcomings. The identification of all compounds responsible and controlling their amounts present in the preparation can be done routinely. The same technique allows for the identification of prognostic and diagnostic biomarkers in patients. That way the patients who are not suitable for the trial as well as the placebo effect can be eliminated. This way, clinical trials can be made more effective and avoid the pitfalls that masked the efficacy of the drug.
Synthetics and biologics
However, the pharmaceutical industry has no interest in going back to plant-based therapies. Synthetics and biologics keep them happy. But our situation as a country is different, we have a lot to gain by bringing Ayurvedic practices to the twenty-first century. Primarily, a sizable percentage of people depend on this system. They will benefit from having medications with proven safety and efficacy and knowing that they are not taken advantage of by snake oil paddlers. They will not waste their hard-earned money on worthless products by falling for flashy advertisements. Second, it will add value to products sold as dietary supplements and nutraceuticals and help bring much needed foreign exchange. Third, it will be possible to give legitimacy to therapies for chronic conditions for which there are no good therapies in western medicine and develop healthcare tourism.
The development work will provide plenty of opportunities for academic institutions to do applied research, provide training, and opportunities for gaining recognition through publications and patents. We have an advantage as we have a wealth of information and a history of practice. There will be other opportunities in the supply of raw materials: growing medicinal herbs instead of low-margin traditional crops.
This should be a collaborative effort of a consortium of industrialists, ayurvedic practitioners, academic and research institutions. The reader might think that this writer is trying to predict the future. No, no, no. I have written about things that have been around for 15 to 20 years. Designer drugs will arrive someday. The founders of Ayurvedic system thought about it in their own way; just as Buddha analysed the human cognition that neurologists are just beginning to find out. This is not a project that has to be started from nothing; the bulk of the work has already been done, there is a wealth of scientific literature, and there are plenty of low hanging fruits to be had. This is a plea to the academics of the of the country. Think of the generation after the next, do not pander to the past. The future of energy is not about fission, it will be fusion. The first commercial scale plant will come online soon. Despite the present questionable reputation, the world herbal products market is worth over $ 180 billion in 2023. It is projected to grow to $433 billion by 2033. Shouldn’t we try to capture some of it in a respectable way? (Concluded)
from The Island https://ift.tt/OTL0Pjx