Rishi Sushruta (800-600BC):
“Ekam shastram adhiyano na vidyat shastra nischayah”
“One may not get accurate or complete knowledge of subject by only one type of approach. Therefore, different streams of knowledge should be considered together to achieve optimum results”
The Ayurveda Developmental Therapeutics Programme (ADTP), created in 2018 by the Open Health Systems Laboratory, started as an international collaborative effort aimed at exploring the role of Ayurveda in cancer management and therapy. It is essential that Cancer be treated as one of the Global Grand Challenges in health in order to effectively an urgently address the tremendous global cost in terms of the suffering caused by morbidity, mortality and care economics. Recognizing the current limitations of allopathic medicine and the vast potential of Ayurveda in the treatment of cancer as documented in ancient Indian texts and by modern practitioners of Ayurveda, a multidisciplinary and multisystemic approach tackling the problem from different perspectives and through the coming together of diverse expertise was perceived to be the ideal path towards a common goal. This coming together of expertise – Allopathic clinicians, Vaidyas practicing Ayurveda and scientists from various fields has given shape to the collaboration that is ADTP.
The program has now expanded its scope to include other diseases where Ayurveda holds potential.
ADTP’s overarching goal is to bridge Ayurveda and conventional western medicine, foster collaboration, build evidence-based practices, and ultimately integrate Ayurveda into mainstream healthcare. The program emphasizes the importance of creating a scientific foundation for Ayurvedic principles to gain wider acceptance in the global medical community.
ADTP and Whole Person Health
While the concept of holistic medicine where the mind and body are treated as a whole and where both internal and external factors are taken into account is an integral part of the principles of Ayurveda, conventional/western medicine subscribes to the reductionist view where treatment often comes down to the single molecular level. Investigations and clinical trials have been largely restricted to single component studies in western medicine. It is therefore noteworthy that the National Center for Complementary and Integrative Health, NIH, has recently introduced the concept of Whole Person Health with funding available for research in whole person health and treatment (NCCIH Strategic Plan FY 2021 -2025). It recognizes that health is dependent on multiple factors and studies and trials based on multicomponent treatment modules addressing different components of health and disease of the subject as a whole will be encouraged. The NCCIH is of the view that “evidence-based complementary therapies should be integrated with and not used as an alternative to conventional medicine”. It was with a similar vision and goal that ADTP was created in 2018.
History and Initial Meetings
ADTP was created during an Indo-US initiative between scientists from both countries interested in pursuing collaborative research in radiation therapy - from brachytherapy to hadron therapy, including combined modality therapy with novel agents such as Ayurvedic compounds, immunotherapy, new biologics, and conventional therapy.
The first in person meeting of this initiative was held on May 9, 2018 in New Delhi.
One of the major recommendations was to focus on Ayurveda and its scientific evaluation as a modern therapy.
Participants in the discussion:
- Dr. Vijay Bhatkar, Chancellor, Nalanda University, Chair of the IUS-ARC Working Group.
- Anil Srivastava, President OHSL, Coordinator of the Working Group
- Dr. Rajendra Badwe, Director, Tata Memorial Centre, Mumbai
- Dr. Jeffrey Buchsbaum, Medical Officer, Radiation Research Program, National Cancer Institute, National Institutes of Health, USA
- Dr. Norman Coleman, Associate Director, Radiation Research Program (RRP) National Cancer Institute, National Institutes of Health, USA
- Dr. Debasis Dutta, Scientist G, Ministry of Electronics & IT (MeitY), Govt. of India
- Dr. GK Rath, Chief, Dr. B.R. Ambedkar Institute Rotary Cancer Hospital & Head, National Cancer Institute, Jhajjar (NCI), Delhi
- From the Indian government:
- Dr. Rajiv Kumar, Vice Chair of NITI Aayog
- Dr. K. VijayRaghavan, Principal Scientific Advisor, Government of India
- Vaidya Rajesh Kotecha, Special Secretary, Government of India, Ministry of AYUSH (Ayurveda, Yoga and Naturopathy, Unani, Siddha and Homoeopathy)
- Dr. Manoj Nesari, Advisor International Cooperation, New Initiatives, Laboratories, Pharmacopoeia and Research, Ministry of AYUSH.
ADTP Roundtables
The initial ADTP roundtable meetings in December 2018 and February 2019 brought together experts from different disciplines including Ayurvedic physicians, Allopathic oncologists, biomedical scientists, computational scientists and pharmacologists to brainstorm on the path ahead for collaborative research that could emerge between Ayurveda and conventional western medicine.
The ADTP consortium is mentored by Dr. Vijay Bhatkar, architect of the first supercomputer in India and a thought leader in the field of Ayurveda. He is the founder of the Center for Development of Advanced Computing – CDAC. Dr. Bhatkar is currently Chancellor, Nalanda University; technical advisor for the National Supercomputing Mission (NSM); and Chief Mentor, Multiversity Pune.
Core goals of ADTP:
- Creating a scientific evidence base for Ayurveda in cancer
- Understanding biological processes at play - Using whole systems approach to understand principles and mechanisms in Ayurveda
- Developing effective therapeutics
- Developing processes for clinical trials that work keeping in mind the holistic principles of Ayurvedic therapy
- Understanding the strengths and limitations of each system
leading to a synergistic/complementing or integrated treatment of disease - Capacity building in terms of infrastructure and trained scientific manpower
- Wider acceptance of Ayurveda based on evidence
Ultimate aim: to alleviate suffering / benefit the patient
The goals of ADTP may be realized through research that falls broadly in the following five areas:
- Creation of a computable resource of Ayurvedic knowledge and its biological mechanisms
- Clinical studies and trials
- Digital twins and virtual clinical trials
- Basic science
- Drug discovery and development
Creation of a Computable Ayurveda Knowledge Resource
Leading Towards:
- Integration of knowledge from Ayurveda and Western Medical Science
- Understanding complex biological interactions that result from Ayurvedic treatment
through application of Data Science approaches - The ability to simulate disease, treatment and drug interactions in silico -
digital twin models - Virtual humans – virtual clinical trials
- Drug development from existing knowledge
- Newer therapeutics
- Predictive, personalized, precision medicine
Ongoing Projects
1. Decoding Sanskrit texts in Ayurveda using Natural Language Processing and Large Language Models:
There exists a large volume of complex text on Ayurveda that is not humanly possible to read and integrate in its whole by any one scholar or Ayurvedic physician. Ayurveda is captured in structured Sanskrit text and necessitates a thorough knowledge and scholarship in both Sanskrit and Ayurveda. These texts are written in a form that requires specialized interpretation that could be computationally possible through tools that decipher the language and tools that would interpret the text in a contextual manner. The information of the texts cannot be simply translated into other languages as words and verses in the text are dependent on those in the preceding verses/sections. The collection of texts are structured with knowledge generated through their integration. A computable form of this knowledge will capture the knowledge from Ayurveda texts, integrate related concepts, and facilitate its use. The aim is to create a computable form of the knowledge represented in the diverse collection of Sanskrit texts that captures the collected knowledge of Ayurveda and its practice using Rule based, Natural Language Processing and Large Language Model approaches to drive context-based translation of Ayurveda texts. This would also allow those who are not versed in Sanskrit to interpret Ayurveda texts firsthand. This endeavour requires close collaboration between computational linguistics experts, Sanskrit scholars, Ayurveda scholars and computational experts.
Collaborators include
- Mandar Bedekar, KLES Kankanwadi Ayurveda College, Pune
- Yogesh Bendale, Rasayu Cancer Clinic, Pune
- Kenneth Buetow, Director, Center for Evolution and Medicine, Arizona State University
- Niladri Chatterjee, Indian Institute of Technology, Delhi
- Oliver Hellwig, Researcher, University of Düsseldorf
- Sudipto Kaviraj, Columbia University
- Amba Kulkarni, University of Hyderabad – Lead Scientist
- Manoj Nesari, Advisor, Ministry of AYUSH, Government of India
- Koninika Ray, Open Health Systems Laboratory
- Anil Srivastava, Open Health Systems Laboratory
2. Digital documentation of records of cancer therapy by Ayurveda
One of the most crucial requirements is that of documentation of the treasure of knowledge and information that already exists. There is an enormous amount of patient data that is scattered in various forms with various Ayurvedic Vaidyas and in various regional languages. They may be audio recordings, written documents or digitized. With each Vaidya such patient information may run into thousands. Hence it is a rich repository in need of scientific collation, documentation, digitization and analysis that has the potential to lead eventually to an understanding of the biological basis, process and outcome of therapeutic interventions in cancer. This repository combined with other digitized knowledge collated could be used in decision making systems and simulation models using data mining and machine learning tools/AI enabling clinicians to make intelligent treatment decisions. These may also lead to new therapeutics or newer ways in which management of cancer may be addressed.
A team of vaidyas, biomedical scientists, computer scientists and data collectors are working closely together in order in order to achieve these goals. The idea is to be able to create datasets that will be wide-ranging and comprehensive to the extent possible. Issues around data sharing and usage will be addressed. There is a need for the various groups engaged in similar efforts to join forces in order to capture and achieve a much larger pool of knowledge through case histories.
Collaborators include:
- Kenneth Buetow, University of Arizona, USA
- Vitthal Huddar, All India Institute of Ayurveda, Delhi
- Ganesh Karajkhede, Rasayu Cancer Clinic, Pune
- Geetha Krishnan GP, World Health Organization, Geneva - Advisor
- Vidyadhar Kumbhar, Sunad Ayurved, Pune
- Archna Mathur, Ex Dabur Research Foundation, Delhi
- Lakshmi Panat, Centre for Development of Advanced Computing, Pune
- Koninika Ray, Open Health Systems Laboratory – Lead Scientist
- Manju Singh, Indian Institute of Technology, Delhi
- Sujata Vaidya, Supra Health Solutions, LLP, Pune
3. Whole Systems Approach towards Ayurvedic treatment – observational study and multiomic analyses to understand underlying biological interactions
Meaningful research to understand the science of Ayurveda cannot follow the reductionist mode in light of the principles of Ayurvedic treatment where equilibrium is sought to be brought about by treating the person in a holistic manner and not targeting the disease itself. The answer to this lies in a systems approach where pathways and their interactions and networks can be studied in their entirety. Information from perturbations and activation of the immune system, epigenetic patterns, metabolic events, microbiotic world, neuronal and endocrine systems and other networks in the body in health, disease conditions and treatment will give valuable insights into the biological system in health and disease. These would be also be invaluable for prediction and prevention of disease, designing effective treatment regimes and much more. Therefore the focus of research moves away from single component clinical trials and drug interactions towards a comprehensive omics research. Collation and integration of these various sets of information at the systemic level and how they interact as a whole is the focus of our research.
Koninika Ray, Open Health Systems Laboratory – Lead Scientist
Plant Based Drug Design
4. Harnessing Medicinal Plants for Novel Drug Development Against Breast Cancer
Various active compounds derived from medicinal plants have been evaluated for their efficacy and tolerance in the treatment of breast cancer. Some of these plant species, including Taxus baccata (paclitaxel, docetaxel), Podophyllum peltatum (etoposide), Camptotheca acuminata (camptothecin) and Vinca rosea (vinblastine, vinorelbine) have well recognized antitumour activities against breast cancer and have been evaluated in clinical trials. For example, results from recent Phase II/III trials have established docetaxel as the most active single agent in the treatment (first or second-line) of advanced metastatic breast cancer.
The current proposal aims to utilise knowledge gained from Ayurveda and naturopathy for possible interventions in breast cancer in order to identify more effective and more economical candidate/s with fewer side effects. To achieve this, plants have been identified using the Indian Ayurvedic knowledge system. These plants are reported to possess chemo-preventative and chemotherapeutic properties and are commonly used in traditional medicine as adjuvants in breast cancer therapy.
Multidisciplinary techniques will be used to identify effective interventions against breast cancer through in vitro assays and in vivo animal models. In a parallel approach, systems biology methods will be used to develop the core disease interaction network. The information obtained will help in identifying key genes whose dysfunction or dysregulation plays a role in disease onset and progression and also optimum targets for the plant-based drugs.
Collaborators include:
- James Gomes, Kusuma School of Biological Sciences, IIT Delhi,
- Ashok Patel, Kusuma School of Biological Sciences, IIT Delhi – Lead Scientist
- Koninika Ray, Open Health Systems Laboratory
- Manju Singh, Morarji National Institute of Yoga, Delhi, India
Advisors:
- Gordon Cragg, Natural Products Branch, Developmental Therapeutics Program, National Cancer Institute, NIH
- Shanker Gupta, Chemopreventive Agent Development, National Cancer Institute, NIH
- David Newman, Natural Products Branch, Developmental Therapeutics Program, National Cancer Institute, NIH
5. Anti-cancer Properties of Phytochemicals
Use of herbal medicines for therapeutic purposes has a long recorded history. Despite therapeutic potential, these traditional medicines are not accepted globally because of the unknown composition and mechanism of action. Therefore, a rigorous analysis by modern science is required in order to provide a proof-of-concept for their therapeutic efficacy. In line with this, the project looks into bioactive compounds from natural sources as therapeutic agents against cancer. An in-silico pipeline will be developed using existing databases of plant-derived molecules and biological targets. Additionally, methods that are under development at FNLCR within the ATOM project will be used to develop an enhanced workflow that will significantly reduce the time required and cost incurred compared to conventional drug discovery methods.
Collaborators include:
- Priyanka Banerjee, Institute of Physiology Charite
- Anagha Bhuvanagri, Data science intern, Open Health Systems Laboratory
- Jaspreet Kaur Dhanjal, Indrapratha Institute of Information Technology Delhi - Lead Scientist
- Dimple Khona, Kaiser Permanente
- Ana Maria Lopez, Jefferson Health New Jersey, Sidney Kimmel Cancer Center
- Cezary Mazurek, Poznan Institute, Poland
- Amita Pathak, Open Health Systems Laboratory
- Koninika Ray, Open Health Systems Laboratory
- Amit Saxena, Centre for Development of Advanced Computing Pune
- Eric Stahlberg, Frederik National Laboratory for Cancer Research
- Anil Srivastava, Open Health Systems Laboratory
6. QAICan: Quantum enhanced AI based Discovery of Plant-Derived Anticancer Compounds
In the realm of drug discovery, particularly in the field of oncology, the identification of potent and safe compounds remains a significant challenge. Traditional methods are time-consuming and resource-intensive, often leading to suboptimal outcomes. This project, "QAICan: Quantum-Enhanced AI for Plant-Based Anticancer Compound Discovery," seeks to address this critical issue by harnessing the power of quantum computing and artificial intelligence (AI) to revolutionize the process of discovering plant-derived anticancer compounds.
The proposal is towards a solution that synergistically combines quantum computing and AI techniques to expedite the search for plant-derived anticancer compounds. By leveraging the inherent capabilities of quantum computers to analyse complex molecular interactions, the potential anticancer properties of these compounds can be efficiently predicted. The AI-driven approach further refines the predictions by incorporating large-scale data analysis and machine learning algorithms. This unique combination of QAICan with AI empowers prediction of anticancer properties with higher accuracy at a significantly faster pace. Additionally, the efficiency of this approach could potentially reduce the costs associated with traditional drug discovery methods.
A functional prototype of the QAICan platform has been developed. While further refinements are ongoing, the pipeline's core components are operational, showcasing the feasibility and potential of our approach.
Core Collaborators:
- Amit Saxena, Centre for Development of Advanced Computing, Pune (C-DAC) – Lead Scientist
- Jaspreet Kaur Dhanjal, Indrapratha Institute of Information Technology Delhi
- Eric Stahlberg, Frederik National Laboratory for Cancer Research, USA
- Anil Srivastava, Open Health Systems Laboratory
Collaboration through ATOM – Accelerating Therapeutics for Opportunities in Medicine
ATOM is a Public Private consortium with the mission of transforming drug discovery by accelerating the development of more effective therapies for patients (atomscience.org). It does this through the linking of high performance computing, a collection of diverse biological databases and emerging biotechnological capabilities. The Frederick National Laboratory for Cancer Research (FNLCR) is one of its founding members.
OHSL has signed an MoU with FNLCR. Virtual Clinical Trial Technologies and medicinal plants and natural products for drug discovery fall within the MoU’s ambit.
OHSL has created a consortium of scientists who will be working on various proposals related to plant based drug discovery through this international collaboration. This group has been meeting every fortnight to discuss individual expertise and research. Project collaborations are expected to emerge from these discussions.
Coordinators for ATOM collaborations:
- Eric Stahlberg, Frederik National Laboratory for Cancer Research, USA
- Anil Srivastava, Open Health Systems Laboratory