Personalised Medicine

Words: Dr S CHAKRABORTY & Dr R CHAKRABORTY

The kaleidoscopic rainbow synthesis is much more than its seven explicit colours; it epitomises a host of wave lengths of diverse coloured light waves stratified into seven distinctive hues.

The plotting of the human genome has, in like manner, allowed us to understand numerous possibilities and deviations that exist in the genome of one single species ever since life began. With more and more perfections in molecular methods, there has been a glut of scientific data in the last twenty years.

The emergence of molecular and genetic medicine has led the way to fulfilling the need for understanding illnesses at the cellular and molecular level — as also devise a tangible, individualistically themed tool for diagnosis, prognosis, prevention, and treatment of a condition that lies contrary to a state of well-being.

It is challenging to billet updated information about disease mechanisms in the existing disease classification systems based on signs and symptoms. Most often, several disease subtypes having distinctive causes, at the molecular level, are clubbed as a single disease. On the contrary, there is a void in linking different diseases that share a common molecular cause too. Yet, the best thing is we possess a somewhat inadequate, yet a roseate, perception of what it all signifies.

Crux Of The Matter

The most significant shortcoming that hinders the pace of development of molecular medicine is incomplete scientific understanding. Scientific materialists are yet to build up a consensus about certain common conditions, influenced by environmental and social factors and/or coupled to the expression of several genes for patient management — for wellness, or to treat their illnesses. Understanding the molecular genetic patterns of the individual looking for a cure through these sophisticated tools are, however, expensive in practice under the roof of a modern healthcare management systems and pretty difficult to match with a reference frame due to a multitude of diversities in human genome as well as their manifestations [complex phenotypes].

The recalibrating of a person’s pathological condition into an ideal well-being state becomes multifactorial and immensely complex. The complexity usually begins with the imbalance between the need of personalised medication, or therapy, and its holistic approach. It is, therefore, imperative to clarify higher freedom of living systems. Hence, in the energy-time uncertainty relation, bringing in a multiplier freedom factor with Planck’s constant would yield high value for biological systems in contrast to the value [unity] obtained for physical systems. The basic features of life could then be explained, in effect, by studying the dynamics of such a system.

Indian medical science — ‘Ayurveda’ meaning ‘knowledge of life,’ or ‘knowledge of longevity’ — defines life as a dynamic system where harmony between chemical and physical processes lead to a ‘healthy’ state of the individual, while the emergence of discordant notes brings illness. For 3,500 years, or more, Ayurveda has addressed the issue of wellness of the human population on the basis of chemical and physical processes called prakriti.

The Principle Of Prakriti

The prakriti is the summed up phenotype — a basic constitution type of every individual that covers multiple attributes, like physicality, parental lineage, likeability, diet and lifestyle, environmental influences and susceptibility to disease.

Prakriti of any individual is determined by thorough evaluation of balance among three components, vata, pitta and kapha, collectively. This is termed as tridosha, which works in harmony to maintain the individual’s well-being and governs defined physiological and phenotypical manifestations.

Just like the array of seven colours of the rainbow, Ayurveda constitutes seven possible prakritis, depending upon the constitution of the individual, or combinatorial proportions of the term in each individual to place them in any one class, viz., vata, pitta, kapha, vata-pitta, pitta-kapha, vata-kapha and vata-pittakapha. This stratification is free of any ethnic, racial, gender, or geographical boundaries. It can, therefore, be applied to the entire human population to scientifically probe the existence of any possible genetic, or molecular, correlations with the distinguishable phenotypes of people belonging to the seven different prakriti types.

Ayurveda conceives of a four-dimensional definition of health [this is a far smarter definition than the one put forward by modern medicine], because a balanced state of somatic and psychic humours [doshas], digestive capacity [agni], body tissues [dhatu], excretions [mala], kriya [physiological activity] and soundness of soul [atma], sensory organs [indriya], and mind [mana], actually defines health [ayus]. According to this perspective, Ayurveda is concerned with measures to protect health [ayus], which includes healthy living, along with therapeutic measures that relate to physical, mental, social and spiritual harmony. Understanding the inner harmony of nature [prakriti] is the philosophical basis of the age-old, yet evergreen medical science of India.

Albert Einstein, in an article of scientific faith, says, “Without the belief in the inner harmony of our world there could be no science. This belief is and always will remain the fundamental motive for all scientific creation.” So, the path of unification of personalised [bespoke] medicine and Ayurveda can be found in its fundamental principles. Like personalised medicine, Ayurveda is not a ‘one-size-fits-all’ system and its regimens are tailored to each individual’s unique body constitution. The focus of Ayurveda is on both patient and disease. Ayurveda may, therefore, hold the key to unlock certain simple, also profound, solutions that can be complemented, or integrated, judiciously to minimise complexity. 

Discussion 

To validate the genetic and molecular basis of prakriti classification, a handful of dedicated attempts were made. Some studies tried to draw attention by pointing out the association of both specific genes and genomic variations with the different phenotypes representative of different prakriti types.

As many as 251 genes have been found to be differently expressed between prakriti groups. Probable correlation among genotypic and expression difference versus prakriti phenotypes were postulated by studying gene polymorphisms of CYP2C19, HLA-DRB1 and EGLN1 genes. Identifiable differences in allele frequencies of common variations in 14 single nucleotide polymorphisms of five genes [FAS, AKT3, FBN2, EGLN1 and RAD51] were postulated to be a probable predictive marker for differential responsiveness of people belonging to different groups towards environment, drugs and diseases. Differences were pointed out in transcription profiles of pooled RNA from different prakriti groups to distinguish core biological processes between the groups. A few earlier studies also attempted to draw viable psychological and biochemical differences within the groups.

Initial Ayurgenomics studies generated valid reasons to initiate further research to establish possible genetic and molecular basis of this classification system, adopted by Ayurveda, in order to make testable predictions for placing a specific individual correctly to a specific prakriti type as a step forward towards personalised medicine. USFDA reports positively the concept of personalised medicine as age-old — one that can be traced back to the core concept of Ayurveda, where treatments were designed in a different way for each and every individual, or uniquely customised for the person to be treated. Evaluation of a person’s prakriti has remained the quintessential first, or primary, step of this customisation.

Diagnosis in Ayurvedic medicine is based on a two-fold approach: examination of the patient and ascertaining the constitution of the individual and status of health and vitality; and, examination of disease, while defining its stage, based on its acute and chronic state.

Types of treatment followed in Ayurveda includes: avoidance of disease causing and aggravating factors [nidan parivarjas]; purification treatment [shodhana]; palliative treatment [shamana]; prescription of diet and activity [pathya vyavastha]; psychotherapy [satvavajaya]; and, rejuvenating protocols [rasayana].

Ayurveda uses whole crude plants, metals and mineral drugs having a mixture of several ingredients. It uses plant drugs, either in single form, or in complex compound formulations of several herbs and plants mixed together.

We could not even possibly touch the tip of the iceberg of promises that has remained hidden in this ancient science with revelations of this primary report suggestive of the scientific foundation flowing underneath the clinic to laboratory, or reverse pharmacology-based healing practices, under the name of Ayurveda, which is usually met with scepticism by scientific materialists. If only we could make ourselves valiant enough to research beyond our comfort zone and begin analysing and justifying the actions and promises of Ayurveda, under the strictest monitoring of current science, we might soon be able to detect certain diseases, even at their very early stage, which is otherwise unrecognisable in current diagnostic practices. In this current age of unimaginable increase in costs of drug development, uncontrollable rise in the phenomenon of multiple drug resistance and diminishing numbers of molecules discovered efficacious without producing severe adverse drug reactions, Ayurveda surely stands a chance to be explored in every possible way by patrons of current science, particularly those who possess a broad holistic and optimistic view to fighting health problems — both persistent and unforeseen by diving deep into molecular and genetic levels and hoping to cure it.

As in our lab, we try to find insights on a plethora of antibiotic resistance by several pathogenic and non-pathogenic bacteria and probable measures to keep them at bay. We’ve used as a last resort antibiotic drugs to crude herbal preparations only to find promising results from the Ayurvedic formulation, eloquently documented in ancient literature.

By applying simple biotechnological approaches, in combination to Ayurveda, we have also been able to decipher mechanisms of action of plant drugs in single form, or poly-herbal fermented preparations, which not only became capable of inhibiting biofilm formation of Pseudomonas aeruginosa, or restrict quorum sensing of Chomobacterium violaceum, but also significantly inhibited several natural isolates found to possess resistance towards different classes of conventional antibiotic drugs. Attempts have been made to check the activity of such Ayurveda-based drugs against various kinds of enteropathogenic metalloβlactamase producing organisms, and to identify probable mechanisms of action[s] with the help of standard scientific methodology currently adapted in the pharmaceutical industry and laboratories across the globe.

Research findings will be published as soon as proper scientific basis could be found in the unfolding of the molecular pathway of drug action and collation of pharmacodynamic and pharmacokinetic data for any possible complementary augmentation of current conventional antibiotic therapy. 

Conclusion   

The silver lining at the time of numerous health hazards reaching a new high is reminiscent of one dire need of the hour — to explore the essence of Ayurveda with every available tool of modern science, viz., genetics, molecular biology, drug discovery, bioinformatics, analytical chemistry, pharmacogenomics, clinical practice and diagnostics and to utilising every possible health benefit hidden benevolently since ages that are unfortunately bulldozed by ignorance and scepticism of modern science which is, in turn, grossly embedded in scientific materialism.

Dr S CHAKRABORTY, PhD, and Dr R CHAKRABORTY, PhD, are with Omics Laboratory, Department of Biotechnology, University of North Bengal, Raja Ramohunpur, District Darjeeling, West Bengal, India. This article was first published in Journal of Molecular & Genetic Medicine, August 2017, 11:3, under Creative Commons Attribution License.

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