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- Herausgeber: Bentham Science Publishers
- Kategorie: Fachliteratur
- Sprache: Englisch
Precision Medicine and Human Health covers several aspects of precision medicine in 20 edited reviews by researchers and healthcare professionals. The breadth of information provided by the contributors aims to familiarize readers with basic and applied research in personalized therapy.
Starting with an overview of the subject and its relationship with epigenetics, the book progresses into advanced topics that explain its wider applications. The use of precision medicine in treating different diseases such as protein misfolding disorders, gut ulcers and their effect on the gut microbiome, cancer treatment (for hepatocellular carcinoma, breast cancer, and oral cancer), fibromyalgia, high altitude sickness, and multiple sclerosis is explained. The book also covers modern therapeutic techniques to administer personalized therapy, including epithelial-mesenchymal therapy (EMT), circadian clock modulation, and artificial intelligence and phytoconstituents. The next chapters cover advanced technologies that are crucial to precision medicine, such as nanomaterials and advanced drug delivery systems. A concluding chapter on the therapeutic use of tannins in precision medicine rounds up the contents.
Key Features:
- Features 20 focused chapters contributed by scientific experts
- Introduces readers to basic concepts in precision medicine
- Covers the application of precision medicine in treating different diseases
- Showcases several techniques used in experimental and clinical precision therapy
- Explains modern technologies in precision medicine
- Caters to a wide readership with introductions, structured headings, and references
This is an informative reference for healthcare professionals in clinics and hospitals and any scholar who wants to learn about basic and applied knowledge in precision medicine.
Readership
Healthcare professionals and scholars who want to learn about basic and applied knowledge in precision medicine.
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Veröffentlichungsjahr: 2024
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FOREWORD
Precision Medicine seems to be a new adage in the world of Medical Science. However, a careful analysis of human civilization from across the globe suggests that almost every civilization has been health-conscious and requires medical attention. Historically, the most reliable and single source of all the medicines were plants, which were carefully selected, propagated and used in different forms. American Indians in the USA used plant-based medicines for relieving pain. Approximately, 40% of all modern drugs are plant-based. Among the 252 essential chemicals designated by the World Health Organization, 11.1% are sourced from plants, while 8.7% originate from animals. Currently, the United States employs approximately 19,000 FDA-approved prescription drugs, with several of them having their origins rooted in the animal kingdom. This suggests that almost 50% of all the drugs are either from plants or animals and perhaps many more may be discovered in due course of time.
The concept of precision medicine has already gained momentum over the world. Simultaneously, medical science has made remarkable progress using the data from the field of Omics, cell and tissue engineering, and gene therapy. The progress and success with molecular taxonomy and tissue expressions in genetic variants have brought confidence in precision diagnosis, efficient prognosis, prevention and effective treatment. We do not have a cure for all the diseases, but are on the right track of passing on the benefits of new knowledge and technology to the patients and their families.
The book Precision Medicine contains well organized 20 chapters covering a wide range sub-disciplines. An overview of several important topics in addition to a critical appraisal on precision medicine has been provided. This initial attempt in the country shall pave the way for more such books on specialized sub-disciplines in future. Advances in today’s medical sciences has provided a scope for new drug molecules, next generation vaccines, stem cell and gene therapy, robotic surgery and other high-end medical intervention. A careful analysis of drug molecules and finding the drug target in the body without any side effects are the areas that still warrant relentless research and innovation.
The present book on precision medicine is the brain child of Farzana Mahdi and Abbas Ali Mahdi, who have shown exemplary courage, determination and concern to provide the best possible care to the patients. Era University has a well-known and highly respected medical college. During the upsurge of Covid-19, more than 3200 patients were cured and the success rate was 98.5%. This is an achievement that has been duly acknowledged by the honourable Governor of Uttar Pradesh.
Farzana Mahdi and Abbas Ali Mahdi are hard core academicians, distinguished biochemists, capable administrators and great mentors. Both believe in quality research and transparent dealing with excellent academic records to their credit; publishing papers in high impact factor journals. They are well connected with the global body of scientists and keep an eye on the emerging advancements in the area of biomedical research. Farzana Mahdi has successfully helmed the Era University as a Vice Chancellor during the pandemic of Covid-19, and Abbas Ali Mahdi is the current Vice Chancellor of the university.
It is gratifying to mention that all the chapters in the book, one way or the other are related to Precision Medicine. I am very hopeful that this book would fuel the thoughts of academi- cians, clinicians and researchers alike transgressing all the sub-disciplines of biomedical research eventually culminating into a better human health care system.
PREFACE
Writing a book on an upcoming topic like precision or personalized medicine (PM) in the context of human health is both rewarding as well as challenging. The origin of such a book is related to an International Symposium that was held on June 24, 2022, at the Department of Molecular and Personalized Medicine, Era University, Lucknow.
During the course of extensive deliberation, it became clear that we need in-depth additional information, not only regarding the diseases and their causative factors, but also about the overall background of the patients encompassing lifestyle, nutrition, age, comorbidity, previous history of the disease, demography, epidemiology, living condition, environmental, social and economic status, gender, marital status, physical and physiological attributes, mutational landscapes of the diseased gene, genetic background, upbringing, region, religion, faith, culture, tradition, familial dis/harmony, marital incompatibilities and overall awareness towards a disciplined and healthy life. Longevity has always been an enticing proposition for mankind since the dawn of civilization. The quest to live forever is still cherished in almost all the societies of the world. The dollar wellness industry thrives on this psyche and that would continue to grow because the demand for such products never seems to be ending.
As the situation stands now, much of the medical issues may be circumvented employing the approach of molecular and personalized medicine. This will require additional biomedical research, keeping in view the patient’s background information and careful titration of the prescribed medicaments. Perhaps, many medicines may not be needed and only a few ones would be enough since the diagnosis will be based on the hard core molecular and “ics” data facilitating the physicians and clinicians to make the correct decision at the right time. With concerted efforts on this line, precision medicine will not only see the light of day but will provide health to all even in the fall flung areas of the country harvesting the power of digitalization, telecommunication and Artificial Intelligence. It is envisaged that the proposed health card (made at the time of birth as proposed in the first chapter) of the patient will carry all the relevant background data in the form of a QR code only to be accessed by authorized clinicians and physicians across the globe. This simple but reliable trick would provide past medical records instantly and do away with many social evils, false claims and impersonation augmenting much-needed transparency in the human health care system.
The present narrative embodied in this book is a biological and biomedical symphony based on research, innovation, experience, and detailed deliberation emerging from the conference, symposium and scientific meetings all culminating in the PM. This encompasses different aspects of life that we come across rather routinely not realizing that many of these events affect our health. Of course, the vicissitudes of life also prove to be blessings in disguise, making a person, careful, strong and optimistic. In conclusion, the growing consensus is that one should be aware of the wide conundrum of health issues and follow the path of a disciplined life. This may not guarantee health, happiness, overall wellness and much-desired longevity. Nonetheless, it would drastically reduce the disease burden and occurrence of negative events in life that in turn would percolate down the ladder leading to robust health. Finally, if we seek peace in life, then we must start believing that peace begins from the self which in turn can be spread in the family, society, state, country, continents, and finally across the world. Needless to mention, a peaceful and relaxed person is a lot less prone to diseases and infection than the one who has an agitated mind. Thus, those of us who preach peace but do not practice will not be able to see the desired results.
This book, Precision Medicine and Human Health, has a total of twenty chapters spread across the spectrum of disciplines. The book includes some of the areas that were less represented earlier in the medical literature. The first chapter dealing with precision medicine provides a critical appraisal encompassing all the key areas that relate to human healthcare systems. For example, emotions, social interactions and life experiences culminating into overall happiness play an important role in the life of a person. Thus, an emotionally strong and happy person is usually healthy. Since everybody, whether diseased or healthy, has a unique genome, this uniqueness must be utilized in selecting the drug molecule, dose, and its long-term effects. Healing and cure strategies should address the root cause of the problem and not the symptoms only to provide short-term relief. Similarly, repurposing of the drug should be explored to cover a much wider number of diseases, cutting down the cost of the development of medicine. Finally, clinicians and doctors should be sensitized to the concept of precision medicine and its sub-disciplines. The medical field, besides being a deep, very deep science is also an art starting from how to deal with diverse types of patients of different backgrounds and educate them by instilling a sense of confidence and then to cure the disease. Clinical psychologists and genetic counsellors particularly in a hospital set up can play their roles too to achieve this goal. Healing requires a combination of medical treatment and a positive environment to achieve faster recovery and long-term benefits for patients.
The second chapter deals with the significance of epigenetics, gene function and putative change or modification in the DNA's sequence. Genes are prone to changes that are brought about by a number of mechanisms encompassing gene conversion, exon/intron reshuffling, alteration in the mutational landscape, and copy number variation. In addition, repeat DNA sequences tend to expand or shrink changing the topology of adjacent genes resulting in their altered functions. Alterations in gene activity, especially those that are brought on by epigenetic errors, frequently cause genetic diseases. Researchers are particularly interested in how epigenetic modifications and mistakes affect gene function, protein synthesis, and human health. It is envisaged that a deeper understanding of the epigenetic modification of the genome or its aberration would augment our understanding of the function of the normal and diseased human genomes.
The third chapter is on Hepatocellular carcinoma (HCC) which is the most common malignancy and is the third leading cause of cancer-related death worldwide. Most HCC patients are diagnosed at the middle or advanced stage, thereby losing surgical resection opportunities. Due to disease heterogeneity, standard treatments such as chemotherapy or radiation are effective only in some patients. Tumors can have underlying genetic differences and may express different proteins across the spectrum of patients. At this juncture, how the PM can provide a better alternative is indeed thought-provoking. Precision medicine relies on matching a patient's molecular profile to an effective and targeted therapy. In clinical practice, the shift from stage oriented to a therapeutic-oriented approach is necessary to direct the selection of HCC treatment towards the potentially most effective option on an individual basis. The clinical application of discoveries in tumor biology holds the promise to improve the treatment outcomes for cancer patients on a large scale. This chapter discusses precision medicine for HCC management and highlights the completed or ongoing clinical trials of novel therapies for treating patients with advanced HCC.
The fifth and sixth chapters are devoted to protein biochemistry encompassing its various forms under varying physical and physiological conditions including folding and misfolding resulting in a wide range of debilitating disorders. These diseases are characterized by the deposition of insoluble plaques consisting of amyloid fibrils rich in β-sheet structures. Many natural proteins form amyloid fibrils or aggregated disease-specific proteins causing human diseases. The role of amyloids and their mechanism of formation, as well as the methods for detecting various types of aggregates, has been examined and discussed. Despite visible progress in the field of biochemistry, we still have questions regarding the aggregation and co-aggregation of protein molecules. Proteins are functional in their three-dimensional forms. The free amino group of the protein in the body when interacting with the carbonyl group of the reducing sugar follows the Maillard reaction to produce hazardous by-products, referred to as advanced glycation end products (AGEs). Studies have shown different aggregation pathways leading to fibril formation. Thus, the development of large number of therapeutic proteins is envisaged to complement the requirement of precision medicine.
Chapter seven relates to Helicobacter pylori in the human gut biomes playing an important role in our health and wellbeing. Helicobacter pylori (H. pylori) is a Gram-negative, microaerophilic, and slow-growing bacteria, colonized in more than half of the world’s population. This bacterium has co-evolved and migrated with humans from East Africa, the first birthplace of Homo sapience, about 58,000 thousand years ago. Special properties of H. pylori, like urease, helical shape, and motile flagella, make it a successful resident in the human stomach under extreme stress conditions. The presence or absence of H. pylori in the stomach has a good and/or bad relationship with humans depending on host genetic susceptibility, immune responses, and environmental conditions. Usually, H. pylori-infected people are asymptomatic; however, about 20% of infected people develop gastric diseases like peptic ulcer (10-15%), gastric adenocarcinoma (1-3%) and mucosa-associated lymphoid tissue (MALT) lymphoma (1%) that are common to elder people. On the other hand, people who have no H. pylori infection are more susceptible to other diseases like gastric esophageal disease (GERD), oesophagus carcinoma, diabetes mellitus, and asthma. Clinical manifestations in the infected individuals greatly vary geographically due to the high level of genetic diversity in the bacterial genome and several virulence factors. Eradication of H. pylori via antibiotics and proton pump inhibitors is the complete cure for the disease. However, an increase in resistance against antibiotics and lack of effective vaccines are still some challenges to combat the infection. In this context, the effective precision medicine would be the vaccine. This chapter provides an insight into host-pathogen interactions, persistence, prevalence, and pathogenesis of this bacterium in the context of human health and precision medicine.
Chapter eight is devoted to breast cancer which is most common among females. Current data shows more than 1 million women worldwide are affected about ~400 000 patients die every year. Partial success has been achieved by mammography and adjuvant treatment. However, incidences and mortality both are increasing. Of the several sub-categories, one is triple-negative breast cancer (TNBC). This is defined by a lack of expression of oestrogen and progesterone receptors and human epidermal growth factor receptor 2 (HER-2). Several approaches have been undertaken both for speedy and accurate diagnosis and precise treatment. In this context, the precision medicine approach may be of great relevance in ameliorating the suffering of the patients from the menace of breast cancer. However, it may be noted that several drug molecules and strategies need to be developed to cover different stages of breast cancer before a respite may be achieved.
Chapter nine focuses on depression, a pervasive, arduous psychological condition with profound neurological ramifications. Many individuals suffering from depression undertake a recurring or persistent therapy that correlates to a decline in cognitive processing. The underpinning of the exact aetiology and pathogenesis of melancholy is probably the outcome of a variety of mechanisms. These include physiological, behavioural, and socioeconomic variables, all playing their roles. Multiple therapies, medications and medical interventions are employed but depression has yet to find its match in the context of precision medicine. One option is to search for a more effective drug molecule befitting to all the symptoms of depression. The other approach is to find a cure from herbal formulation. In any event, both approaches need additional research, innovation, and development for ultimate effective interventions.
One of the aspects of precision medicine is to make use of artificial intelligence (AI) which is discussed in chapter ten. The digital ecosystem of AI will have global outreach evoking expert opinion from clinicians in serious conditions of the patients. The AI is envisaged to be the game changer, particularly in case of cancer, which is described as a heterogeneous cellular conglomeration comprising many dissimilar subtypes. The AI involves the use of deep learning which is a part of artificial intelligence (AI) that permits an algorithm to learn itself via the knowledge acquired from a large set of instances that determine the predicted outcomes. The use of AI is continuously growing for the prognosis of various diseases enabling pathologists to accurately diagnose various diseases, and classify them into grades and subtypes keeping in view the process of invasion, mutations, and metastases. AI also contributes to the area of precision medicine to overcome drug resistance and relapse of diseases. This chapter outlines various illustrations for the uses of AI in oncology research, together with circumstances in which deep learning has adequately addressed the difficulties that were earlier assumed to be unsolvable. AI also focuses on resources and datasets that can assist in developing interconnections with AI's intricacies in disease investigation. The expansion of advanced computational methodologies and AI are envisaged to facilitate interactomes studies and help significantly gain insights into the field of oncology fulfilling the concept of personalized medicine.
Chapter eleven relates to Fibromyalgia Syndrome (FMS) which has attracted much attention, especially with the gene discovery pushing towards a newer understanding of disease biology. Potential candidate genes found to be associated with fibromyalgia are SLC64A4, TRPV2, MYT1L, and NRXN3. Fibromyalgia is a widespread musculoskeletal pain disorder accompanied by fatigue, sleep, memory and mood issues. FMS amplifies painful sensations by affecting the way the brain and spinal cord process painful and non-painful signals. Some targeted treatments are now available improving the FMS patients on a short-term basis. This chapter highlights the key breakthroughs focusing on technologies that touch upon personalized or precision medicine in FMS. If FMS is related to brain and spinal cord functioning, work on this line using animal models would prove to be a rewarding proposition as the use of human patients would pose a logistic problem.
The time code is expressed in the form of circadian clocks composed of many transcription, co-activator, and co-repressor factors. These aspects have been covered in Chapter twelve. The transcription-translation feedback loops generated collectively by these factors regulate daily ~24-hour rhythms in physiology, metabolism, and behaviour across divergent phyla. Genome-wide studies reflect that chronic disruption of circadian rhythms provides a plinth for the occurrence and progression of multiple diseases across our lifespan. Increasing epidemiological and experimental evidences are confirming that circadian clocks are compromised in cancer and several other diseases. Altered expressions of circadian clock components are likely to be associated with the onset and progression of cancer and cardiovascular diseases. The concept of targeting circadian clocks at the molecular level is rapidly evolving and opening a new therapeutic window in cancer. Here, we discuss the approaches and recent advancements that have been made for the identification and development of clock-modulating small molecules bearing drug-like properties for the therapeutic management of cancer. Thus, this chapter is envisaged to augment the concepts of precision medicine in general and circadian-related system anomalies in particular.
Of the several diseases that have become the cause of concern, Multiple Sclerosis (Mus) is one that is an autoimmune inflammatory disease affecting roughly 2.8 million people worldwide which is covered in Chapter thirteen. Mus is a highly heterogeneous disease in term of course, clinical symptoms and drug response. The exact pathogenesis and aetiology of this disease remain unknown. The lack of successful treatment can be explained by the heterogeneous nature of MuS with patients exhibiting widely disparate clinical features and progression pattern resulting in phenotypic heterogeneity. With the introduction of Omics approaches, personalized medicine has gained momentum revealing hitherto unseen elements of illness causation, initiation and progression. This chapter highlights the potential role of genomics, transcriptomics, proteomics and metabolomics in MuS for possible identification of biomarkers facilitating and augmenting the concept of precision medicine.
The chapter fourteen deals with the clinical challenge related to metastasis of cancer cells to distant organs forming a secondary tumor. Many cancers are prone to metastasis due to epithelial-mesenchymal transition (EMT), which confers motility and invasive properties to the tumor. EMT is also responsible to chemotherapy resistance and facilitates metastasis by generating cancer stem cells (CSCs). Therefore, the EMT may be an important candidate for therapeutic potential for personalized cancer treatment. This chapter discusses approaches for the design of EMT-based personalized therapies in cancer, summarize the evidence for some of the proposed EMT targets, and review the potential advantages and limitations of each approach.
Yet another rather common cancer is the oral cancer covered in Chapter fifteen. Oral cancer is a type of head and neck cancer mainly caused by poor oral hygiene, alcohol and tobacco abuse, and promotes HPV infection. The conventional approaches for the treatment of oral cancer often rely on surgery, chemotherapy and/or radiotherapy. Now, the precision medicine, with the advent of newer diagnostic techniques, enables healthcare professionals to diagnose the disease early and treat the patient with appropriate medicines with the optimized dose. Targeting specific proteins, such as EGFR and HER2 to suppress tumor growth or make cancer cells more susceptible to the immune system’s combat mechanism is also discussed. In addition, this chapter has an overview of various drugs that are being used to treat patients who are positive for HER2 and EGFR. Various challenges and limitations of precision medicine and future prospects for research in this area are highlighted.
The chapter sixteen and seventeen are devoted to herbal medicine. The treatment using plant based medicaments has been prevalent in almost every civilization such as Sumerian, Maya, Red Indian of USA, Greek, Roman and Egyptian for the past seven thousand years. India is blessed with rich medicinal plant biodiversity. Food harnessing and garnishing have become standard practice to enhance the taste and look. Some of the herbs are used directly as food whereas others are used as food additives. Simultaneously, a large number of Phytoconstituents have been characterized for their medicinal properties. In these chapters, Phytoconstituents used for herbal formulation have been discussed with their detailed properties. It is envisaged that such information would be of great use to ameliorate the diseases ensuring better health complementing the concept of personalized medicine.
The Chapter eighteen deals with the human habitat where there is paucity of oxygen (hypoxia). Hypoxia is a condition wherein an organism or a cell of an organ does not receive adequate levels of oxygen to carry out normal life processes. The ability to sense oxygen level and respond appropriately is termed “oxygen sensing” that is used to describe the biological effects of hypoxia. Hypoxia is involved with multiple diseases from high altitude pulmonary oedema to cancer. The oxygen sensing molecular networks is crucial for survival and has a notable impact on human health systems. A very important niche of hypoxia is the study of environmental stressor also called high-altitude hypoxia. High-altitude hypoxia holds multiple molecular similarities with diabetes, cancer, obesity and other diseases like COPD. In addition, unregulated exposure to hypobaric hypoxia is known to directly cause high altitude illnesses like HAPE/HACE. Acclimatization with the high altitude is known to prevent the occurrence of high-altitude illnesses. This chapter highlights the occurrence of hypobaric hypoxia, its socio-economic impact, molecular underpinnings and correlation with inflammation, cancer, diabetes, obesity and possible therapeutic approaches to these diseases.
Chapter nineteen discusses the advances in nanotechnology and its therapeutic potential. This chapter highlights the promising role of Nanomaterial in Precision oncology where the conventional therapy dwindles. Moreover, the emerging role of Precision Medicine in dentistry genetic diseases and Cystic fibrosis is highlighted which was once a nightmare but now is completely curable with the boon of Precision Nanomedicine. Chapter twenty provides an overview of the current state of the art in nanotechnology-based drug delivery systems and their potential applications. It discusses the various types of nanoparticles that are currently being used or developed for drug delivery, including liposomes, dendrimers, and polymeric nanoparticles, and highlights their advantages and disadvantages. It also covers some of the key challenges and risks associated with the use of nanotechnology in drug delivery, such as toxicity and regulatory issues. Finally, the article explores the future prospects of nanotechnology in drug delivery and highlights some of the areas where further research and development are needed. It is envisaged that this technology will facilitate augmentation of precision medicine for better human health care across the spectrum of diseases.
In this book, chapters have been linked with PM. The book also highlights hitherto less trailed aspects of Ayurveda, a treasure trove of our country. Logic dictates that if already available tried and tested herbal formulations are given as an additive or supplementary medicaments to the patients, that may speed up the process of healing with no or minimal side effect. Simultaneously, research may be conducted to uncover active factors from the still uncharacterized medicinal plants and herbs, synergizing their strength to make them more potent to be used as drug supplement. It is envisaged that the book will provide a conceptual framework for clinician, doctors and researchers in the field of biomedical research augmenting the human health care system and providing additional impetus for future research and innovation complementing the Precision Medicine.
DEDICATION
List of Contributors
Personalized Medicine (PM) A Critical Appraisal
Syed Tasleem Raza1,*,Saliha Rizvi2,Allal Ouhtit3,Farhan Ali4,Sher Ali5Abstract
Personalized medicine, also referred to as precision medicine, deals with a clinical model that delineates patients into different groups based on their ethnicity, lifestyle, food habits, medical history, drug reaction, comorbidity, the robustness of the immune system, age, gender, and proneness to infection, overall psyche and attitude towards life. Further, emotions, social interactions and life experiences culminating into overall happiness play an important role in the life of a person. Thus, an emotionally strong and happy person is usually healthy. Taking all these above factors into consideration and with accurate diagnosis, a drug may be prescribed more in tune with the uniqueness of the patient’s genome. Since everybody, whether diseased or healthy, has a unique genome, this uniqueness must be utilized in deciding the drug, dose and its long-term effects. Healing and cure should address the root cause of the problem instead of working only on the symptoms to provide short-term relief. In addition, repurposing of the drug which is not an old concept should also be carefully explored because with this approach, a large number of already available drugs may be used for a much wider number of diseases than the medicine originally developed for. This will also help reduce the cost of the development of medicine. Finally, clinicians and doctors should be sensitized to the concept of precision medicine and its less obvious sub-disciplines. This is envisaged to provide better, more accurate diagnosis and may result in better treatment. The medical field, besides being a deep science is also an art starting from how to deal with diverse types of patients of different backgrounds and educate them all the way to instill a sense of confidence and then to prescribe the medicine to cure the disease. Seemingly, within the realm of precision medicine, it is a huge task. However, it is possible to collect and analyze diagnostic data to reach a consensus. This would require the involvement of clinical psychologists and genetic counselors in a hospital setting ensuring that patient care is holistic, taking
into account both the physical and psychological aspects of health. This integrated approach can lead to improved patient care and long-term well-being.
INTRODUCTION
Every human genome is unique as mentioned earlier with respect to its organization, gene expression, regulation, signal transduction, immune system, and response towards different drugs. The genome is a dynamic ensemble of several attributes and constantly adopts and adjusts to maintain cellular homeostasis. During the course of duplication of about 7 billion diploid sequences in a single cell, the genome must ensure that it remains error-free. However, the genome is constantly getting affected by the environment and therefore the possibility of newer mutations may not be ruled out. It is therefore relevant to uncover genetics and environmental bases of diseases. How the concept of PM is viewed across the globe, is another important issue because the world has become small though the healthcare system has become big. Since quality management of patients is possible only when we have a deeper understanding of the disease heterogeneity together with the genome heterogeneity of the patients, we have included demography, epidemiology, ethnicity and genome heterogeneity in our discussion. Finally, we have taken into consideration the prevalent healthcare system and its management, not only in India but in other countries as well. It is envisaged that our attempt at PM will enhance awareness of this theme evoking sufficient interest amongst clinicians and doctors to become more multidisciplinary in their approaches, bringing several healthcare systems on a single platform. This will be a win-win situation for both doctors and researchers. Since medicine is manufactured by pharmaceutical companies, it would be befitting to keep them in the loop so that more fruitful results are obtained. In the context of PM, drug repurposing and titration are two main aspects that must be seriously considered as a topic of research. When adequate data is available on this line, innovation will continue to trickle into the realm of the human healthcare system. Finally, we all agree that prevention is better than cure; we should therefore try to sensitize the masses to make a change in their lifestyle from an unhealthy one to a healthy one. If this calls for some sacrifice at a personal level, so be it. It has been largely believed that our life revolves around genetics and environment with a ratio of 50:50. However, a recent closer scrutiny suggests that the role of genetics is only 10% and the rest all is the environmental impact. Thus, the scope of the environment in the human health care system is expanded with new found knowledge. Clearly, the environment includes a lot more things than we have envisaged so far. Cancer now is considered a preventable disease but 1 million Americans and more than 10 million people worldwide are at risk of cancer. Significantly, 5-10% of cancers have a genetic basis; the remaining ones are based on lifestyle and environmental factors. The lifestyle includes cigarette smoking, diet (fried food meat), alcohol, sun exposure, environmental pollutants, infections, stress, obesity, and lack of physical inactivity. About 25-30% of cancer-related deaths are due to tobacco alone, 30-35% are linked with diet, about 15-20% are due to infections and the rest are because of radiation, noise pollution, lack of sleep, and substance abuse. Prevention is possible in most of the cases, like quitting the use of tobacco, regular uptake of fruits and nuts, moderate or better still, no use of alcohol, restricted intake of calories, use of whole grains, use of timely vaccination, avoidance of too much sun exposure, regular exercise and routine medical checkup. Such changes amongst masses may reduce the genome heterogeneity facilitating the development of PM. There has been a history behind the origin of precision medicine but the concept is now gaining momentum with the availability of better research tools, more awareness, and faster communi-cation.
Origin and Concept of Personalized Medicine (PM)
A teenage boy and his grandmother would not buy the same clothes because their bodies will have different size requirements. However, during sickness, they may receive the same medical treatment and so will everyone else. At this juncture, the differences and now fully established genome heterogeneity are not taken into consideration.
That’s because even the world’s best scientists and doctors do not fully understand how different people develop diseases and respond differently to treatments. The “one-size-fits-all” approach in medicine has been going on but this has never been rationalized let alone challenged. Why population study, demography, epidemiology, population structure, genetic makeup, genotypes, mutational load, food habits, region, religion, susceptibility and resistance, liking and disliking, thought processes, customs and tradition, choice of mating partners, day-to-day activities, the timing of food intake and retiring to bed, disciplined/ undisciplined lifestyle and change in the weather are not taken into consideration before prescribing the medicine. This is because what is practiced by the doctors is what they have been taught. Perhaps doctors do not have time to think beyond their defined hours of duty. During their studies, they were not asked not to think and use their own imagination. The so-called common sense is highly uncommon, because, in the majority of the cases in every field, this is simply lacking. Thus, based on broad population averages, and decade-old drug trials, medicine is prescribed. There is no information on how the same medicine in two different persons will be metabolized. However, after the intake of the drug, this can be ascertained by analyzing urine samples from the patients. Nonetheless, this approach has never been part of the drug trial. This traditional practice often misses its mark because each person’s genome makeup and genetic background are very different from the other persons. These points are important because they all affect our health. The concept based on precision medicine is moving us closer to a more precise, predictable and powerful healthcare system that is customized for an individual patient. Our growing understanding of genetics and genomics would allow us to gain an insight into health drive, disease and drug responses in each person. This would enable doctors to ensure better disease prevention, more accurate diagnoses, safer drug prescriptions and more effective treatments for many diseases. Thus, personalized medicine is going to stay because its time has come.
Issues Related to PM
There are several issues that are related to precision medicine. These are highlighted here under with the assumption that they evoke the imagination of clinicians and doctors.
Shift the Emphasis in Medicine from Reaction to Prevention Because Prevention is Better than Cure
If the disease symptom is detected early, perhaps the disease may easily be managed. Besides, textbook knowledge, overall experience plays a great role in correct diagnosis. This is particularly important for some very serious or accidental cases. Based on the blood or urine analysis, medicine is prescribed but hardly ever, attempts are made to uncover the causative factors taking cellular homeostasis into consideration. This includes genetic background, lifestyle, ethnicity, resistance or susceptibility to the diseases, past medical history, and physical and emotional quotients that may be collectively or individually responsible for altered blood or body chemistry. Even the living and work conditions tend to affect the health of a person. When there are too many variables, finding a consensus becomes a challenge. However, concerted attempts on this line would start showing the results. Thus, challenges may be taken more like an opportunity to nurture and nourish this upcoming branch of biomedical science.
Susceptibility Prediction of an Individual to Diseases
Susceptibility of an individual to a disease may be due to several reasons including genetics, environment, allergy, compromised immune system, age, gender, emotional quotient, wrong diagnosis and incorrect medicine or its wrong dose. Thus, improved disease detection (genetic analysis), family background information, and disease history including genomepatri may all be helpful. Some people are severely affected by a mere change in weather since the environment itself continues to change with respect to the presence of virus, bacteria, allergens, pollutants and a variety of immunogens. Similarly, food allergy is equally common resulting in food phobia amongst the affected people. Not withstanding these challenges, this area deserves exploration for a broader understanding of the genome interaction with the environment and vice versa. For example, if a strong association of food or pollen allergy with a particular ethnicity is established, that would accordingly facilitate the prognosis and diagnosis. The development of data on this line would then allow focusing on other variables in search of consensus. Eventually, this work is envisaged to uncover the much-desired population structure in the context of the occurrence of diseases and disease susceptibility.
Pre-empt Disease Progression
Disease pre-emption involves prior appropriation of the diseases. Thus, if a disease is diminished even up to 50%, that too will be helpful. The aim is not to allow the disease to spread and cripple the person. For example, if a person develops oral cancer and shows leukoplakia, should he be immediately rushed to the Operation Theater? Perhaps not, if the oral cancer may be controlled by drugs, the surgical operation may be avoided. Better still, if the awareness program is conducted on a war footing, particularly in the village set up to apprise the ignorant ones about the danger of tobacco consumption, this menace may largely be reduced. Disease pre-emption may not be feasible for all diseases. However, wherever possible, that should be done. Similarly, prenatal diagnosis will help in the context of suspected genetic anomalies. A severe case may be considered for medical termination of pregnancy after due deliberation and consultation of the doctors with parents. While pursuing this area, a patient's medical history may faithfully be recorded which will be part of the medical database for futuristic medicine.
Customization of Strategies for Disease-prevention
A large number of infectious diseases and the ones that are waterborne may be managed by awareness programs and community health services. The doctors may aim to reach the far-flung areas in a mobile van to spread the message and educate the masses on how not to get infected by taking certain precautions. In extreme conditions, water can be boiled and filtered before its use or supplemented with chlorine tablets. The water source or the wells in the village may be sanitized with a recommended dose of potassium permanganate. The diseases that are caused due to unhygienic conditions may be curtailed by practicing overall sanitation. This requires a large-scale awareness program focusing on far-flung areas of the country. In principle, this aspect may further be facilitated by print and electronic media focusing particularly on the uneducated people of the society. Simultaneously, local, state, and central governments may gear their machinery to ensure that basic living facilities are available in the far-flung areas of the country.
