Prakriti and genetics


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Prakriti and genetics

  2. 2. ACKNOWLEDGEMENTSIt is a matter of great privilege for me to work under the able and highly exceptionalguidance of Dr. R. Sreekumar, former Head of the department, Department of RogaNidana, Govt. Ayurveda College Kannur, who has nurtured my capabilities andalways gave me ample freedom. His energetic smile, optimistic attitude, criticaljudgments and above all trust in my abilities kept me going and ultimately towardsthe attainment of this goal. No less had been the incessant help and constant encouragement providedby my co-guide Dr. Moinak Banerjee, Scientist – E1, Human Molecular Genetics lab,Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram during the course of mystudy. His scholarly guidance, experienced words, meticulous practical training,disciplined and virtuous nature, unlimited sincerity and affection towards studentshad always inspired me and I feel extremely fortunate to be his student. Words are not enough to express my sincere and heartfelt thanks to Dr. V.N.Parameswaran Potty and Dr. K.V. Subhadra Antherjanam andDr. P.K.V. Anand for their immense help in my studies. Their devotion and dedicationto work, passion for knowledge, inquisitive mind and scientific attitude have made aneverlasting impact on me and boosted my confidence. My special thanks to Dr. K.Sankaran, Director, Ayurveda Medical Education, Dr. John K George, Head of thedepartment, Dr. S. Jayadevan Asst. Professor, department of social and preventivemedicine, Academy of Medical sciences, Pariyaram, Dr. V.K. Ajithkumar, Readerand Dr. S. Gopakumar, Tutor of my department for their kind concern, criticalcomments, wise counseling and timely tips which are invaluable.I adore and respect them for their ‘Never say no’ attitude and magnanimous natureand I owe them a lot. 2
  3. 3. Former Director Dr. R.V. Thampan, Director Dr. M. Radhakrishna Pillaiand Scientists from other departments of RGCB and especially to research scholars,Mrs. Resmi Thomas, Miss. Neetha Vijayan, Mrs. Linda Koshi, Mr. Chandrashekharand technical assistants Mrs. Sudha B. Nair, Mrs. Bindu Ashokan, Mr. Antony K.Pand the summer trainee students who attended the HMG lab from variousbiotechnology colleges, for their timely assistance in the lab and their invaluable helpand moral support. I also extend my sincere thanks to my batch mates Dr. Mukesh,Dr. Viswanath, Dr. Sudarkkodi, Dr. Surabhi Mishra, Dr. Senthil Nathan,Dr. Surama Mishra, Dr. Anjali, Dr. Abhilash and Dr. Bindu Mary Mathew and otherP.G scholars of various Ayurveda Colleges for being there, whenever I was in needthem the most and for their constant support and encouragement. Nevertheless, I am not missing out this opportunity to acknowledge andappreciate some of my colleagues and very good friends like Dr. Nandalal,Dr. Sunil Babu, Dr. Madhu, Dr. Prabha Manish, Dr. Gopikrishna, Dr. Annie Yohanan,Dr. Vijay, Dr. Prasanth Kekuda, Dr. Brijula, Dr. Anupama,Dr. Yogeswar Pawale, Dr. Arbind Kumar Jha, Dr. Bindu, Dr. Sudhagopal,Dr. Eby Abraham, Dr. Vibhu Khanna, Dr. Namratha, Dr. Pradeep, Dr. Rejitha, Dr.Vidya Menon, Dr. Sarita Mohanta, Dr. Manas Ranjan Debta, Dr. Priya,Dr. Ananthalekshmi, Dr. Nandakumar Sahni, Dr. Shambhu Sharan, Dr. Sijin, and Dr.Pramod whose infinite love and affection had always strengthened my determination. Words are meaningless to express my unaccountable feelings to my fatherSri. K.V. Neelakandan Namboothiri (late) and mother Smt. C.N. Arya Devi (late);sisters, Mrs. K.N. Anjana Sree, Mrs. K.N. Archana Sree andMs. V.P Aparna; brother in laws Mr. Sivanandan and Mr. Narayanan Namboothitri, 3
  4. 4. and nephew Mr. Vijay Sankar and niece Ms. Swathy for their belief in me, kindunderstanding, patience and perseverance and above all in making me what I amtoday. I owe them more than anything else in the world. Special thanks are also dueto my beloved wife Mrs. Shreeja Devi and daughter Ms. Devi Nanda without whosehelp and support, none of my dreams would have ever come true and without whomlife would have never been the same for me. The wealth of information provided by our college library also deservesspecial thanks. Dr. K.N.AJITHKUMAR 4
  5. 5. INTRODUCTIONH IS EXCELLENCY THE PRESIDENT OF INDIA Dr. A.P.J. ABDUL KALAM in his Address at the Inauguration of the Govt. Ayurveda College HospitalComplex and Interaction with the Students at Govt. Ayurveda College, Trippunithura,Ernakulam, Kerala on 17th December 2005 talked on the topic “Traditional Medicine:Our Strength”.He pointed out that the traditional system of medicine like Ayurveda, Siddha etc.have advocated and practiced preventive and curative medicinal recipes specific toindividuals. The body, mind, food and environment were looked at holistically tosuggest a preventive or curative approach to health. He also stressed the need forcollaborative research of Ayurveda and biotechnology. Dr. Kalam’s focusing onpersonalized medicine of Ayurvedic system of medicine has invited our attention tothe fact that in this post genomic era, the emerging concept of personalized therapyon the basement of Pharmacogenomics is a re-definition of diseases on themolecular level so that diagnotics and therapeutics can be targeted to specificpatient populations sub-typed on the basis of genetic make-up.India is on a path breaking research and development activities in various areas tocombine the strength of Ayurveda and the power of Biotechnology so as to place thenation in global leadership position in the matter of providing quality traditional healthcare. The National Biotechnology development strategy addresses the utilization ofBiotechnology to add value to our traditional knowledge especially Ayurveda,Siddha, and Unani systems as well as tribal and folk medicine. Medicinal plants arealso prime targets of bioprospecting. Besides, the tool of biotechnology can be usedfor conservation and characterization of plants. Development of plant basedmedicine and mechanism based screening of herbal drugs known in traditional 5
  6. 6. Indian system are included in the strategic action of the National Biotechnologypolicy to get value added drugs quickly. For the Inaugural Address at the “DELHISUSTAINABLE DEVELOPMENT SUMMIT 2003” Vigyan Bhavan, New Delhi,February 6, 2002, His Excellency the President of India Dr. A.P.J. Abdul Kalamselected the topic ‘PROSPEROUS – PEACEFUL – SAFE HUMAN HABITAT’. Whilenarrating the utilization of Biotechnology for wealth generation, he also stressed onintegrative research in Ayurveda and biotechnology and stated that newtechnologies as evidenced by human genome sequencing, proteomics,chemogenomics, ultra high throughput screening is revolutionizing drug discovery1.Medicinal plants offer enormous scope for development of drugs and he highlightedthe need to create database of traditional medicine for specific bioactivity and leadfor development of new drugs. He explained that the North Eastern States of Indiahave got tremendous opportunities for herbal farming and research and that there isan integrated relationship between science, technology, environment, manufacturingand the society.Dr. M.S.Valiyathan has also advocated research on valuable traditional knowledgeand basic principles of Ayurveda, and not just on herbal drug development2. Use of modern technology and Biotechnology has been identified byGovt. of India, Department of AYUSH as a thrust area for 10th plan period forstrengthening the base for sustained propagation of Ayurveda. The objectives andgoals of Kerala Biotechnology policy is also designed to catalyze the development ofAyurveda. The policy, among others, aim to apply biotechnology tools to “ boost thestates renowned health care practice of Ayurveda by synergising traditionalknowledge with the scientific validation and technical product profiling and clinicaldata base and by evolving means to conserve and substantially use one of worlds 6
  7. 7. most valued biodiversity treasures located in the state.” It also aims at creation of anadvanced multipurpose analytical testing and standardization laboratory approved bythe National Accreditation Board for testing Calibration of Laboratories to cater theneeds of Ayurveda and pharmaceutical industry for meeting international standards.Pharmacogenomics – the study of how an individual’s genetic make up affects thebody’s response to treatment or drug - is a rapidly growing science after thecompletion of Human Genome Project was celebrated in April 2003 and it is adeveloping research field still in it’s infancy. Pharmacogenomics hold the view thatdrugs might one day be “tailor- made” for individuals or small populations based ongenetic make up. Modern medicine has developed based on general principles ofphysiology, pathology diagnotics and treatment were as Ayurveda upholds individualphysiology, pathology, diagnostic and personalized therapy. In this post genomicera, the emerging concept of personalized therapy on the basement ofPharmacogenomics is infact, a re-definition of diseases on the molecular level sothat diagnotics and therapeutics can be targeted to specific patient populations sub-typed on the basis of genetic make-up and there by offer the right treatment for rightpatient population individual. The emerging personalized medicine holds the view that environment, diet,age, lifestyle and state of health all can influence a person’s response to health andthat due to genetic variations a disease may manifest itself slightly differently indifferent types of patients. Understanding the genetic make up of an individual is the key to personalizedtherapy. As, at present, there is only limited knowledge of which genes are involvedin each drug response and that many genes are likely to influence a response andobtaining a correct picture on the effect of genetic polymorphisms are complicated, 7
  8. 8. time consuming and expensive, a high speed data mining of both genotypic andphenotypic information is essential for the development of personalized therapy. Inshort, identification and analysis of millions of single gene nucleotide polymorphisms(SNPs) to determine which drug and specific diet are more suitable to a patient isquite impractical. Hence it has become necessary to categorize individuals on thebasis of board phenotypic clusters. Consideration of racial, ethnic and geographicalfactors for classifying phenotypes to be considered collectively for genotyping iscontroversial. Here, Ayurvedic concept of Prakrithi comes in to play. According to Ayurveda, every individual is different from another and henceshould be considered as a different entity. But for diagnostic, prognostic andtherapeutic purposes Ayurveda categorizes human population in to sub-populationssuch as Vatha Prakrithi, Pitha Prakrithi, Kapha Prakrithi or their combinations on thebasis of physical, physiological and psychological characteristics (phenotypes) andcompletely avoid racial, ethnic and geographical considerations. In fact, theaforesaid concept that due to genetic variations, a disease may manifest itselfslightly differently in different types of patients and the same therapy and drug willnot produce equal response in different individuals has well developed thousands ofyears ago in Ayurveda. After analyzing and correlating the varying responses ofindividuals to various factors like drug, food, sleep, sex, exercise, climate,environment, and assessing various physical, physiological and psychologicalcharacteristics (phenotypes) and sub typing the individuals showing similarities in theabove responses and characteristics, the human population is grouped in Ayurvedain to smaller populations and designated as a particular Prakrithi such as VathaPrakrithi, Pitha Prakrithi, Kapha Prakrithi or combinations of either two or three ofthem. Similarly, the body functions, tissues and organs are also sub-typed on the 8
  9. 9. same lines. For example, on the basis of the characteristics the pulse (nadi) iscategorized into Vatha, Pitha, Kapha or their combinations. Based on the smallvariations in signs and symptoms exhibited in the above sub-typed populations,diseases especially metabolic disorders are also sub grouped in to Vathapredominant, Pitha predominant, Kapha predominant or combinations of either twoor three of them. Due to various factors, a disease may exhibit signs and symptomsof Vatha/ Pitha/ Kapha/ their combination predominance in an individual irrespectiveof the type of Prakrithi. One of the basic concepts of Ayurveda is that, if a particular disease havingthe symptamotology of Vatha predominant type is occurring to anindividual/population sub-typed as Vatha Prakrithi and dwelling in a place havingVatha predominance and if the disease is occurring in an organ /tissue of Vathapredominance at a time/season having Vatha predominance, the disease isconsidered of having bad prognosis .The Prakrithi predominance of the tissue, place,time and individual is assessed by specific criteria provided under the basicprinciples of Ayurveda. An individual/population is sub-typed into a particularPrakrithi on analyzing the phenotypic characteristics of that individual/population;and a place by analyzing the nature of micro-climatic conditions, elevation, soilconditions, vegetation, water, air and the phenotypic characteristics itself of theplants and animals of that place, and that of time/season is determined by analyzingthe seasonal/timely climatic factors such as solar radiation, atmospheric pressures(direction of wind), humidity, characteristics of clouds, etc, and the body’s responseto the above factors. Modern biotechnology upholds the view that the collectiveinteraction of about 30000 genes give us life and their normal function keeps the 3trillion – cell human being healthy by producing the right proteins where as their 9
  10. 10. altered function by mutation due to exposure to harmful external and internalenvironments produce wrong proteins that make disease. In short, if the etiologicalfactors provided by place (geopathological), time (climatic) and organism (metabolicand genetic) are highly potential, co-existing and correlating in terms of Ayurvedicprinciples for manifestation of a disease, the severity of the disease thus manifestedis the most, and the disease is most difficult to cure. The genetic make up of thereceptors or its potential and the receptor sensitivity of various factors pertaining totissue, time and place is an important factor that determines the severity of thedisease. Modern western medicine has developed under the influence ofreductionism-breaking down human organism into smaller levels of such as organ,tissue, cell and gene and focus on the diseased part and often treat to suppress thesymptom to get an immediate result rather than a long term process of correcting themetabolic derangement. As a result, a drug therapy or gene therapy targeting onmodification of activities of a cell or group of cells produces toxicity to others and it isestimated that even in most developed countries out of 3.5 billion annualprescriptions 3 billion produces adverse results and the treatment adopted to onedisease give rise to another disease. With a holistic approach, Ayurveda advocatesthe need for micro analysis of the tissue morbidity, the geopathological factors of thedwelling place, the immunological status, the micro climatic elements and how theyinfluence the metabolic activities, the state of digestive and metabolic fire, thegenetic make-up by analyzing the phenotypic characteristics, the state of body thatdepends on the course of time, the state of psyche, life style, food habits etc of apatient for personalized diagnosis and therapy. 10
  11. 11. If the phenotype (outward appearance of an individual as a result ofgenetic make up and environment, i.e. dosha Prakrithi lakshanas) and thecorresponding genotype are correlated by the tools of bio technology, it will not onlyenable to highlight the ever modern principles of the oldest health science, Ayurveda– Puranam cha Punarnavam - but also to generate data to the modern scientificcommunity to classify patients with same phenotypic characteristics into smaller subpopulations defined by genetic variations associated with disease, drug and foodresponse. Such studies will also enable the development of Pharmacogenomics andpersonalized therapy from infancy to child hood more securely and safely in thecradle of Mother Ayurveda. Many scholars and institutions in the field of medicine,biotechnology and policy making are up in arms for research in the field of Ayurvedain the light of modern technology and biotechnology.Dr M S Valiyathan has pointed out the possibility of having genomic counter parts for‘dosha Prakrithi’ mentioned in Ayurveda3. The National Bio-technology Policy stress that the emerging disciplineof Pharmacogenomics combines both InfoTech and BioTech skills in augmentinghigh speed data mining of both phenotypic and genotypic information from welldifferentiated patient populations with a view to evolving new forms of diagnotics andtherapies of personalized medicine. Institute of Genomics and Integrated Biology,one of the premier laboratories under the Council of Scientific and IndustrialResearch, Govt. of India is currently working on the project: “Genotype PhenotypeCorrelation based on the principles of Ayurveda with special focus on Prakrithi”. A perusal of the observations and opinions of profound scholars,research project initiated and proposed to initiate at various national and inter-national institutions in the fields of medicine, bio technology and policy- making 11
  12. 12. attests that my present study which aims to analyze the role of DNA in determiningPrakrithi by conducting Polymerize Chain Reaction studies, to understand thegenetic correlation of various forms of Prakrithi and to develop standards for auniform guide line in analyzing Prakrithi is relevant in the Post Genomic Era and itwill add flavour to all the on going research process for the correlation of Ayur Tech,Bio Tech and Info Tech. 12
  13. 13. PRAKRITHI - A MOLECULAR APPROACHMicrobes developed in toxins become resistant to a considerable extend to thattoxin1. Similarly, zygote developed in a particular environment also become resistantto a considerable extends to that environment. Here the environment of the zygote isan energic template – dosha sthithi2 – emitted and maintained unchanged throughout the span of life of an individual (Janma maranaantharala varthini nirvikarini) bythe interaction of the germ cell genotype (Sukla – Sonitha Prakrithi), climatic anduterine environment (Kaala garbhasaya Prakrithi), the nature of mothers food andpsychophysical activities (Mathraahara vihara Prakrithi) and the nature of Panchabhoothas of the biosphere (Maha bhootha vikara Prakrithi) that are in operation atthe time of fertilization3. The energic template – dosha sthithi – is termed as‘Prakrithi’ that transmits various physical, physiological and psychological phenotypiccharacteristics considered as normal, when compared in relation with the abnormalcharacteristics that constitute the hereditary diseases or Aadi bala pravritha roga.The energic template – dosha sthithi – has two states – normal (Praakritha) andabnormal (Vaikritha). Dalhana in Garbha vyakarana sareera of Susrutha samhitha(verse 63) states that the normal energic template is the cause for Prakrithi whereasthe abnormal energic template causes genetic disorders. The effect of abnormalenergic template in causing deformity is explained on the analogy of the effect of theforce of flood. During rainy season a system of over flowing river water, theembedded woods, rocks and surrounding land is set into action. What variations theresultant force of flood will cause to the shape and size of a tree on the bank that fallinto the river cannot be predicted even if the general behavior of the river, the natureof the embedded woods and rocks and the flood plain are well assessed. Similarly,even though the nature of interacting factors such as the germ cell genotype (Sukla 13
  14. 14. – Sonitha Prakrithi), climatic and uterine environment (Kaala garbhasaya Prakrithi),the nature of mothers food and psychophysical activities (Mathraahara viharaPrakrithi) and the nature of Pancha bhoothas of the biosphere (Maha bhootha vikaraPrakrithi) are well assessed, what variation the resultant abnormal energic template(Vaikritha dosha sthithi) will cause to the phenotypic characteristics of the zygotecannot be predicted, says Charaka in Athulya Gothreeya sareera (verse 30).Charaka considers the zygote as ‘Chatushpadi4’ because it is developed from thefirst four among Pancha bhoothas – Prithwi, Ap, Thejus and Vayu derived from foursources – 1. Sperm (sukra) 2. Ovum (sonitha) 3. Nutrient fluid (rasa) and 4.‘Athma’.Abnormal state of any of the four factors derived from the aforesaid four differentsources may render the zygote abnormal the effect of which will be reflected in theoffspring. “Bija” (Sperm & Ovum) is a collection of functional units, which byrepresenting the structures and features of all parts and organs of an individual iscapable of ensuring the formation of offspring resembling the parents4a. Suchfunctional units are called “Bijabhagas”, which can be more or less similar to the term“Gene” in modern genetics. Hairs on the head, mustaches, hairs on the body, bone,nails, teeth, veins, ligaments, arteries, semen etc, which are stable, have paternaldominance. Muscles, blood, fat, bone marrow, heart, umbilicus, liver, spleen,intestines, anus etc that are soft have maternal dominance. Growth of the body,strength, colour of the body, existence of the body in normalcy and its destruction(decay) are mainly determined by factors derived from rasa dhathu (nutrients frommothers diet). The four factors derived from Athma, are in a very subtle state so thatonly the yogis can perceive it5. Vagbhata explains the transmission of such factorsassociated with Athma to the zygote in the uterus on the analogy of transmission ofenergy from solar radiation through a magnifying glass to the target object (cotton, 14
  15. 15. paper, firewood etc.)6. The abnormalities in the transmitted factors associated withAthma may cause derangement mainly in sense perception and mental activities inviolation of cause and effect theory and is designated as ‘Karmaja vyadhi’. Thepattern of inheritance of the factors associated with Athma is indriyas, theirreceptivity, general knowledge, special knowledge, Ayus (life span), happiness,misery etc. Indriyas are the effect of interaction of the factors associated with Athmawith those of gametes and nutrients. Indriyas and their channels are in the form ofenergy in the brain and are explained on the analogy of the radiations emitted fromthe sun7. Hence a disease can be manifested as Poorvaparaadhaja (Karmaja), orDrishtaparaadhaja (known etiology such as Sahaja/ Garbhaja/ Jathaja/ Peedakrithaetc) or by the combined effect of both (Sankara roga). Hence diseases manifestedwithout a traceable etiological factor of genetic, nutritional, climatic, traumatic originis to be considered as of Karmaja vyadhi caused by the effect of deranged state ofthe four factors associated with Athma. It is noteworthy to mention that these factorscan induce heritable changes in Bija bhagas (genes). Piles can be seen as ahereditary disorder (Sahaja Arsas)8. Here a heritable change occurs in the gene thatdetermines the development of rectal layers. Vagbhata says that this change can beinduced by two factors:1. Psychophysical and nutritional defects of parents transmitted through gametes(MathaPithraapacharatha) 2. By ‘daivam’, which means that, the invisible factors(Susookshma bhoothas) transmitted through Athma. Charaka points out thepossibility of occurring discordance in monozygotic twins due to the effect of athmajabhava in the distribution of genetic material at the time of duplication and zygotic celldivision9. The both factors are simultaneously considered in Ayurveda for diagnotics,prognotics and therapeutics. 15
  16. 16. If the 16 factors10 derived from Sperm (sukra) Ovum (sonitha) Nutrient fluid (rasa)and ‘Athma’ are of normal state, the zygote develops into a normal child. Chart 1: DETERMINANTS OF PRAKRITHI 1 - Mathrja 2 - Pithrja 3 - Rasaja 4 - Athmaja P1 P2 P3 P4 A1 A2 A3 A4 T1 T2 T3 T4 V1 V2 V3 V4 ZYGOTEAgain, the characteristics which we consider as normal and transmitted by differentforms of energic templates can be considered as abnormal, if compared with thecharacteristics of an ideal personality, which infact, is only conceptual as such apersonality can never be seen due to our inability to provide the superiorenvironmental conditions essential for the emergence of such a trait11. In thiscontext, Charaka considers Prakrithi (normal) as Vikrithi (abnormal) and use the termVathala, Pithala, Sleshmala instead of Vatha Prakrithi, Pitha Prakrithi and KaphaPrakrithi. In short, the superior germ cell genotype (Sama Prakritihi) provides healthto the developing embryo (Garbha) and its variations such as Vathala, Pithala,Sleshmala and combinations of either two of them cause varying degrees ofprownness to disease (sadaathura)12. Hence Vatha Prakrithi is considered as Heena 16
  17. 17. (bad), Pitha Prakrithi as Madhyama (better) and Kapha Prakrithi as Uthama (best)and combinations of either two of them (dwantwa Prakrithis) as Nindya (worst)13. So,such individuals are always more prown to diseases, and adverse environmentalfactors can easily trigger corresponding diseases to the embryo or to the individualdepending upon the nature of factors involved. Considering the varying states ofgerm cell genotype, the effect of which is reflected in the physical, physiological andpsychological characteristics of the individual (Phenotype), Ayurvedic genomicsmandate that every individual is different from another and hence should beconsidered as a different entity14. But for diagnostic, prognostic and therapeuticpurposes, Ayurveda categorizes human population on the basis of relativesimilarities in the aforesaid phenotypic characteristics in to 7 sub-populations suchas Vatha Prakrithi, Pitha Prakrithi, Kapha Prakrithi or their combinations of two or all.Infact on microanalysis, Vatha (V), Pitha (P) and Kapha (K) have at least 62 stateson the basis of the percentage of degree to which they combine. Suppose 25%increase = +1, 50% increase = +2, 100% increase = +3 and equilibrium state = 0;whereas 25% decrease = -1, 50% decrease = -2, and 100% decrease = -3,combinations of either two of the doshas renders 18 (9+ and 9-) states and three ofthe doshas renders 26 (13+ and 13-) states and 12 +, =, and – combination states100% increase or decrease of any one of the dosha constitute 6 {3 (+3) and 3 (-3)}other states as detailed in table 1 below: V+1P+2 P+1K+2 V+1P+1 V-1P-2 P-1K-2 V-1P-1 V+1K+2 K+1V+2 V+1K+1 V-1K-2 K-1V-2 V-1K-1 P+1K+2 K+1P+2 K+1P+1 P-1K-2 K-1P-2 K-1P-1 K+1V+2P+2 K+2V+1P+1 V+1K+2P+2 K-1V-2P-2 K-2V-1P-1 V-1K-2P-2 P+2K+1V+1 P+1K+2V+2 P+2K+1V+1 P-2K-1V-1 P-1K-2V-2 P-2K-1V-1 17
  18. 18. V+1P+2K+3 P+1K+2V+3 V+1K+2P+3 V-1P-2K-3 P-1K-2V-3 V-1K-2P-3 K+1P+2V+3 P+1V+2K+3 K+1V+2P+3 K-1P-2V-3 P-1V-2K-3 K-1V-2P-3 V+3 P+3 K+3 V-3 P-3 K-3 V+P0K- P+V0K- V+K0P- K+P0V- P+K0V- K+V0P- V+K+P- V+P-K- P+K+V- P+V-K- V+P+K- K+V-P- V+3P+3K+3 V-3P-3K-3(Charaka samhitha Su. 17/ 40 to 44)In Sama dosha Prakrithi, all the three doshas are in a state of balance essential toprovide superior intra zygotic environment inevitable for its healthy growth andmultiplication. A state of simultaneous provocation of all the three doshas will causedisintegration of the zygote and hence such a Prakrithi does not occur15. Where as,such a state in the somatic cells of the embryo or of the individual will manifest into adisease of bad prognosis (Janma bala pravritha roga)16.A correct perusal of the ancient and modern concepts of hereditary disease revealsthat autosomal recessive inheritance and sex linked dominant inheritance involvesboth Mathrja and Pithrja bija dushti, whereas sex linked recessive inheritance isexclusively Mathrja and all these can be included in Aadi bala pravritha roga.If a woman’s diet and psychophysical practices provokes tridoshas is reflected in thewhole body and also in ovum and uterus. If the dosha provocation is severe, thezygote only disintegrates whereas the provocation is mild, and fertilization occurs,muscles, blood, fat, bone marrow, heart, umbilicus, liver, spleen, intestines, anus etcthat are soft and are derived from the mother, become defective in the zygote as therespective bija bhagas render defective (gene mutation), either completely orpartially. When the bija bhaga that determines the development of uterus and / or 18
  19. 19. ovum of the offspring is subjected to vitiation, it will give rise to a sterile female(Vandhya). If the defect is in garbhasaya bija bhaga avayava, puthi praja (still birth)or neonates with loose body tissues (klinnanga prathyanga)17. It is understood thatDystrophin is required inside muscle cells for structural support; it is thought tostrengthen muscle cells by anchoring elements of the internal cytoskeleton to thesurface membrane. Without it, the cell membrane becomes permeable, so thatextracellular components enter the cell, increasing the internal pressure until themuscle cell "explodes" and dies. The gene that encodes dystrophin is found on the Xchromosome. Duchenne muscular dystrophy (DMD) is one of the most prevalenttypes of muscular dystrophy and is characterized by rapid progression of muscledegeneration that occurs early in life. All are X-linked and affect mainly males — anestimated 1 in 3500 boys worldwide18.When the genes that determine development of uterus, ovum, and that of thesecondary sex characteristics like breast, vagina, linea alba, etc. are rendereddefective super females (sthree akrithi bhooyishtam) called Vaartha19 is born.Vaartha and super females or Trisomy X mentioned in modern genetics showssimilarity. It affects females who have three X chromosomes, instead of the usualtwo. It is the most common X-chromosome disorder in females. Triple X is arandom mutation, usually inherited from the mother. Parents who have a daughterwith Triple X usually do not have to worry about their later children having thesyndrome. The mutation occurs in one in every 1,000 to 3,000 newborn girls, but itis often not diagnosed until later in life. Many girls and women with Triple X have nosigns or symptoms. Signs and symptoms vary a lot between individuals, but caninclude: Increased space between the eyes, Vertical skin folds that may cover theinner corners of the eyes (epicanthal folds), Tall stature (height), Small head, Speech 19
  20. 20. and language delays and learning disabilities. Delayed development of certain motorskills, behavioral problems, seizures, delayed puberty, infertility, rarely mentalretardation20.If a man’s diet and psychophysical practices provokes tridoshas it is reflected in thewhole body and also in genes that determines sperm and testis. If the doshaprovocation is severe, the zygote only disintegrates, whereas the provocation is mild,and fertilization occurs, hairs on the head, mustaches, hairs on the body, bone, nails,teeth, veins, ligaments, arteries, semen etc, which are stable, and are derived fromthe father, become defective in the zygote as the respective bija bhagas renderdefective (gene mutation), either completely or partially. Charaka depicts sterilemale, in relation with sperm and / or testis determining gene. If the defect is insukraroopa bija bhaga avayava, puthi praja (still birth) or neonates with highly firmbody tissues (sthiraanga prathyanga)21.Fibrodysplasia Ossificans Progressiva (FOP) is an extremely rare genetic diseasethat causes muscle to be turned into bone. FOP is an autosomal dominant condition,but most cases are sporadic. FOP patients have a genetic fault, which means thattheir bodies cannot switch off the mechanism that grows the skeleton in the womb.Any small injury to connective tissue (muscles, ligaments, and tendons) can result inthe formation of hard bone around the damaged site. Children are born with acharacteristic malformation of the great toes and begin to develop heterotopic (extra)bone formation during early childhood. Eventually, a second skeleton begins to formthat severely restricts mobility. FOP affects 1 of 2 million people. Because of the verysmall numbers of patients, identifying the mutation(s) causing FOP is difficult. Thereare several genes that have been implicated in the disease process. For example,when the Noggin gene (NOG) is deleted in mice, the mice are unable to stop the 20
  21. 21. deposition of bone, causing an FOP-like disease. Another gene of interest is theBone Morphogenic Protein gene (BMP), which Noggin regulates. Proteins encodedby BMP induce bone formation, and one of their roles is to stimulate the formation ofthe fetal skeleton. In FOP, lymphocytes deliver BMP4 to areas of damaged muscle,and so initiate bone growth rather than aid tissue repair. It is hoped that futurestudies will pinpoint the mutation(s) occurring in FOP and lead to a betterunderstanding of the disease’s mechanism22.When the gene that determine development of testis, sperm, and that of thesecondary sex characteristics like beard, penis, moustache, etc. are rendereddefective super males (purusha akrithi bhooyishtam) called Trina puthrika23 is born.Trina puthrika and super males or XYY syndrome mentioned in modern geneticsshows similarity. An early observation that males with a second Y chromosome, XYYwere found in excess numbers in a maximum-security prison was greatly overinterpreted. Most boys and men with a second Y are normal. The origin of the XYY ispaternal non-disjunction at the second meiotic division, which produces YY sperm.XYY syndrome is a genetic condition in males with extra Y chromosome (in 1 in1000 male births). Symptoms: tall stature (over 6), may including sterility,developmental delay, learning problems 24. Our acharyas have mentioned variousenvironmental factors that induce genetic disorders by causing bijopatapthi andwarns not to indulge such regimns or to avoid such causes for getting a meritoriouschild. It is also adviced to use factors to make beneficial effects in bija bhaga to havean offspring of desired qualities also. Psychic factors like worry, anxiety andemotional upsets etc of the parents may produce changes in bija bhagas the effectsof which are manifested in later generations or results in reduction of phenocopies inthe next generations. Even the mental state of mother at the time of coitus and also 21
  22. 22. during the child bearing period can influence the psychogenesis and even themorphogenesis of the fetus. Positive thoughts and mental wellbeing of the parentsare capable of endowing the gamates with factors essential for the formation of anoffspring with superior health of the body, mind and spirit. Thoughts related tovarious catagories can induce changes in corresponding genes and it will produceharmful or beneficial effects in the physical and mental functions of the offspring. Ifthe parents are constantly given to grief the progeny may become fearful, thin andshort lived. If they think ill of others that may make the offspring antisocial, envious,and subjugated to women. If they indulge in the feeling of stealing that makes theoffspring exceedingly lazy, malicious, and of inactive disposition. If they constantlyresort to anger that makes the offspring fierceful, deceitful, and jelous25. Vagbhataeven dare to say that at the time of coitus if orgasm is occuring to the female first,her mental functions may provoke Vatha and that will induce changes in the spermthat immidiately enters vagina i.e; it will induce changes in the genes that determinethe development of testis and / or sperm, leads to disgenesis or malformation ofseminiferous tubules and vas deferens and will give birth to a child havingazoospermia or aspermia (Vathendriya)26.Sleeping in open air and moving at night alone may result in production of insaneprogeny whereas resorting to abuses and physical hazards may make the progenyepileptic. Alcoholic addicts may make the offspring constantly thirsty, short ofmemory and fickle minded. Intake of inguana fish may make the offspring suffer fromdiabetes, stone in bladder and dribbling of urine. Intake of pork flesh may induceheretable changes that produce redness in eyes, certain obstruction of respirationand excessive roughness of hair of the offspring. Habitual intake of fish may causedelayed closure or non closure of eyelids. Intake of sweet things may produce 22
  23. 23. offsprings suffering from diabetes, obesity, and dumpness. Habitual intake of sourfoods may render the offspring suffer from disorders of liver and spleen (RekthaPitha). Increase intake of salt may result in early onset of wringles, graying of hairand baldness in the child27. It is difficult to depict all such food materials and lifestyles that may produce unfavourable effects in the next generation and this doesnot fall within the scope of this treatise. Most of the diseases having a geneticcomponent are difficult to cure and certain diseases such as cleft pallete and hairlipswere corrected by surgical measures even in ancient times. Some of the inbornerrors of metabolism can be controlled by regular replacement of the missing factorsor by preventing accumulation of toxic metabolites by appropriate manipulation ofdiet and treatment. Stressing the point, prevention is better than cure to avoidgenetic abnormalities, Ayurveda priscribes several regimns if followed strictlyenables to get meritorious offsprings and thus a better and fittest species.Dalhana coments that swabhava bala pravritha rogas are due to the effects ofPrakrithi and indicates the natural or spontaneous occurance of disease. Naturalorganic phenomina such as death, ageing, hunger, thirst, and sleep are included inthis chatagory. They are subdivided into kaalakritha (timely) and akaalakritha(untimely). Since most of the species seen to have a built in survival programmePrakrithi is maintained unchanged through out the span of life. A change in Prakrithiindicates deterioration of survival programme that leads to death. The synonym ofsareera – kaaya and its nirukthi, ‘cheeyathe annadibhi:’ also implies this fact.Cheeyathe by anna means anabolism, in the same way the aadi sabda may includethe inbuilt genetic survival programme. The congenital state of dosha which interactwith genetic material (bija bhagas) for the expression of a particular Prakrithiimposes restriction upon the span of life of an individual. Vatha Prakrithi have short 23
  24. 24. span iof life while Pitha Prakrithi have moderate span of life and Kapha Prakrithihave long span of life.Body of Vatha Prakrithi individuals have lean and tall shape, rough rigid, un-proportionate, asymmetrical, marked with large number of veins and bulged calveswith dusky, cracked and lusterless hair, sole of feet and hands cold to touch.Produce sound from joints while walking with unsteady and swift gait (movements).Eyes are small, round, brown, lusterless, dry, and unpleasant, unattractive with thin,partially open lid while sleeping. They are talkative and use irrelevant, obstructed,interrupted words, in harsh voice. They are fond of music, humor and gambling.Fond of foods – like sweet, sour, salty and hot items. They are cruel, thievish, andungrateful and are non-magnanimous, jealousy, unsteady in courage, memory,thinking, movements, friendship and observation. Their dreams are fearful, anddreams roaming on mountains, dwelling on trees, and moving in the sky.Body of Pitha Prakrithi individual is of medium built with medium strength,symmetrical and proportionate with very loose joints and muscles, agitatedmovements, coppery red palms, soles, tongue, lips and face, hot to touch. Skin iswhitish or yellow with wrinkles, spots or pimples and scanty grey or brown hair. Eyesare thin, small, unsteady, brown or coppery red in colour with thin, few eyelashes,becoming red very quickly by anger, alcohol and exposure to sunlight. The voice isharsh, irritable and high-pitched. They are fond of garlands, perfumeries, and havemoderate sexual and physical strength. Fond of foods – like sweet, astringent, bitter,cold items. They are jealousy, highly intelligent, good behaviour, clean andaffectionate, brave, proud; with helping disposition and quick tempered, but do not 24
  25. 25. attracted by women. Their dreams are frightening, and dreams red coloured flowerslike palasa, forest fire, meteor, lightening, thunderbolt, sunrays and fireBody of Kapha Prakrithi individual is soft, symmetrical, well-defined, good lookingwith long arms, elevated chest, wide fore head, deep-seated, strong, unctuous, well-knit joints and bones and walks with steadiness and firm stepping. The skin colourslike shining of weapons, gorochana (yellowish), padma (reddish), suvarna (golden)with thick curly blue – black hair, slightly hot to touch. Eyes are red at angles,unctuous, wide, and long, with well-designed white and black spheres more withdense and dark eyelashes. Talks less, gentle, and clear with deep sounding voiceslike roaring clouds, ocean, drums or lion. Speaks relevant, not harsh or abusive orharbour enimity. Fond of foods and drinks of all tastes especially sweet, astringent,bitter, hot items, and extra curricular activities like music, dance, drawing, sex, etc.They are mild in nature, very sleepy, patient, magnanimous, courageous, intelligent,truthfulness, foresight, steady memory, thinking, movements and friendship,forgiveness, straight forwardness, obedience, and faithfulness. They dreamreservoirs of water with full of lotus, rows of birds and clouds.Vatha Prakrithi, Pitha Prakrithi and Kapha Prakrithi are known as ‘eka doshajaPrakrithi’ and are otherwise termed Heena (bad), Madhyama (better) and Uthama(best) Prakrithis respectively and combinations of either two of them seen in thesame individual (dwantwa Prakrithis) is considered as Nindya (worst). Combinationsof all the characteristics of the entire first three Prakrithis seen in one individual istermed as Sama Prakrithi and is considered as super, rare or conceptual. Theconstitutional, temperamental, psychological, emotional and social characteristics ofhuman personality are considered in detail in Ayurveda for accurate diagnosis, 25
  26. 26. prognosis and treatment. Hence among under the ten investigation methods, Charaka considers assessment of Prakrithi first. Ayurveda mandates that, the study of Prakrithi should be conducted with special reference to religion (Jati prasakta), family (Kula prasakta), and also on the basis of the influence of geopathological factors (Desanupatini), climatic elements (Kalanupatini), age factors (Vayonupatini), and inividual developmental traits (Pratyatma niyata)28.Prakrithi with reference to religion (Jati prasakta Prakrithi) Seers, sages and visioneers from ancient to modern times have stressed the significance of our thinking and a strong belief in what we think has an influence in molding our character. Religion encompasses a group of individuals having an orchestrated belief system modulated through generations having specific thinking pattern, life style, food habits, recreation etc. It is a common belief that identical twins have exactly the same characteristics through out their lives. Monozygotic twins brought up under different orchestrated belief system of two different religions will exhibit remarkable differences in genomic distribution affecting their gene expression portrait at an older age, though they were epigenetically indistinguishable during the early years of life. All beliefs are basically a thought. It may be our name or an experience, belief is something we have accepted and stored in memory. If the acceptance is unverified and blind, it is a dogma. A set of beliefs becomes a belief system. That such a system has remarkable influence on our bodily and mental health. Ayurveda point out that thought pattern of the parents can influence the morphogenesis and psychogenesis of the fetus. To give birth to a child resembling the individual of a particular race of a particular place, Charaka and Vagbhata advises, that the parents should willfully follow up intentional activity of the mind of 26
  27. 27. that group of individuals having a specific orchestrated belief system and also followthe life style, food habits, recreation etc of that group of individuals. Chakrapaniestablishes the existence of influence of mind upon matter with examples such asejaculations due to sexual feelings, fetal repercussions caused by the emotions ofthe mother, which centers around the non fulfilled desires during the child bearingperiod, oja kshaya (low immunological status) and sukra kshaya (oligospermia) dueto grudge, fear, etc29. Dr. Benson30 writes that, “The potentially destructive stressresponse typically occurs automatically when an outside stress or – such aspressure as work, fear, or anxiety – causes the body and brain to go on full alert.Animals and humans share this stress-response. The relaxation response (by “lettinggo”) is peculiarly human, in that it tends to arise from a specific act of volition or aconscious relaxation strategy.” Placebo effect when combined with relaxationresponse magnifies the beneficial impact on health.The effect, meditation and firm self-confidence have on our health to the extent ofeven affecting the genes is being documented through collaborative research byneuroscientists, psychiatrists and meditation practitioners. Environmental factorsincluding directed thinking appear to have an ability to modify the proteins that act asgates in activating or turning off the genes, thus controlling the gene expression. It isestablished that thought is a form of energy. Directed thought and meditation areshown to have demonstrable influence in changing the neural circuits in the brainoverriding genetic disposition. Confident positive and intense thinking within acarefully orchestrated belief system (not blind dogma) appears to have the potentialof bringing about a transformation in an individual superseding the genetic effects.Individual’s thoughts, whether one is consciously aware or unaware, also effect thegene expression. By creating a facilitating and enabling environment (Satsangatya), 27
  28. 28. it can be possible to alter the program in the genes to the extent that their self-perpetuating character is curbed. Charaka, in Vimana staana 8th chapter - Jati-soothreeya (genetic equations) - proposes performance of ‘Puthrakaameshti’ for thispurpose, where as Susrutha proposes the same in the chapter of Sukla - Sonithasudhi sareera.Current brain research is establishing that brain has tremendous plasticity. This is incontrast to the earlier view of the neuroscientists that the neural circuits, when onceformed in childhood, do not change. “Even though we are born with a set ofinstructions and neuro-signatures, our brains perpetually recruit new nerve cells andnerve-cell activation patterns to handle its daily inputs”.Buddhist meditation technique of “Mindful Attention,” Schwartz (2003)31 could showthrough brain scans the changes that came about in the activity of parts of brain(particularly the caudate nucleus) when his four step therapy was followed by thepatients of Obsessive Compulsive Disorder. He established the plasticity of brain tolearn new things (change the neuronal connections) under the intentional activity ofthe mind. Dr. Schwartz says in Chapter X:“It seems that neuroscience has tiptoed up to a conclusion that would be right athome in the canon of some of the eastern philosophies: introspection, willedattention, subjective state – pick your favorite description of an internal mental state– can redraw the contours of the mind, and in so doing can rewire the circuits of thebrain, for it is attention that makes neuro-plasticity possible. The role of attentionthrows into stark relief the power of mind over brain, for it is a mental state (attention)that has the ability to direct neuro-plasticity. Confident, positive and intense thinkingwithin a carefully orchestrated belief system (not blind dogma) and scientific lifestyles and food habits and other instructions of any religion intended to bringing 28
  29. 29. about a transformation in an individual superseding the bad genetic effects are now a days rarely followed by its followers and therefore the concept of assessment of Prakrithi with special reference to religion has no relevance.Prakrithi with reference to family (Kula prasakta) As in the case of religion, in olden days families were also having scientific life styles, food habits, concept of physical and mental cleanliness, etc. the effect of which are reflected in hereditary and somatic mutations. Hence assessment of Prakrithi with reference to familial practices was also included in the strategy of the olden times. Individual’s born in the family of alcoholic addicts will have the ability to withstand intoxication produced by alcohol when compared to others32. Numerous examples are provided in Ayurvedic literature to support the above view.Prakrithi with reference to geopathological factors (Desanupatini) Study of geopathological factors (Desanupata) is considered as an important factor for the pathophysiological activities of the body. Bhumidesa is classified into three according to its particular features and ecological status – Jangala, Anupa, and Sadharana33. The saint Parasara, in Vrikshayurveda, an ancient treatise on plant science in Sanskrit developed parallel with Ayurveda, also depict land into the above three classes. Instead of Sadharana desa he uses the term Misra desa. Jangala desa is an arid land with thick evergreen forests, huge trees, dry soil, with full of rough and hard granites and gravels; where birds such as quil, francolin partridge, Greek partridge etc inhabits. According to Vrikshayurveda, in Jangala desa, the tract is almost like a desert with scanty vegetation and limited water resources. The soil is sodic (Usavantha) with abundance of gravel and sand. Kadara (Acacia sp. with black heart wood), Khadira (Acacia catechu), Asana (Terminalia tomentosa), Aswakarna (Shorea dalbergioides), Sallaki (Boswellia serrata), Dhava 29
  30. 30. (Anogeissus latifolia), Tinisa (Ougeinia dalbergioides), Saala (Shorea robusta),Badara (Zizyphus jujuba), Somavalka (Ficus dalhousia), Kimsuka (buteamonosperma), Amalaka (Phylanthus embilica), Vata (Ficus bengalenesis), Aswatha(Ficus religiosa), Sami (Leguminous sp.), Kakubha (Terminalia arjuna), Simsapa(Dalbergia sissoo), Yava (Hordeum vulgare), Godhuma (Triticium aestivum), Bajjira(Pennisetum americanum) and various types of legumes as well as annual grows inJangala desa. Due to extremely dry condition of the soil and the natural aridenvironment, among the panchabhoothas, the biosphere is predominant with agni,vayu and prithwi and hence it result in producing plants containing kashaya(astringent), katu (pungent), and thiktha (bitter) sap. Caharaka says that in such aplace Vatha dosha will be predominant, the people are generally strong built andhard hearted. The predominance of Vatha dosha influences the herbs, birds,animals, and human beings and it is reflected in their Prakrithi.Anupa desa is comparatively low place near the sea level with full of trees, coconutgardens etc. the place is surrounded by lakes and rivers with frequent cold winds.The atmosphere is very moist, and herbs and bushes show a very good seasonalflowering tendency. Birds such as flamingo, ruddy goose, cranes, woodpeckers,cuckoos, etc richly inhabit the place. Description of Anupa desa is more or less samein Vrikshayurveda also. Here the land is green grassy and has clusters of reedyplants (Nala), Nelumbo sp. (Kumuda), calamus rotung (vethasa) the soil is clayey.Strong storm like wind laden with heavy moisture keeps blowing. Rows of Hindala(Phoenix paludosa), Tamala (Garcinia morella), Kadali (Musa sp.) and Narikela(Cocos nucifera), Venu (Bamboosa sp.), Vanira (Calamus roxburghii), bordering theriverside present a scenic view. The forestland there appears beautiful withassemblage of various types of trees, shrubs with blossoming young branches. Due 30
  31. 31. to the moist nature of soil and influence of Prithwi and Ap bhoothas, the herbs, creepers and annuals flourishing in the area generally bear sap that tastes sweet or sour. People living there are beautiful, and the place tends to produce predominance of Kapha dosha and it is reflected in the Prakrithi of the Anupa desa inhabitants. Sadharana desa or Misra desa is having mixed characteristics of the above two. The people of this place are fair, strong, and most healthy. In Misra desa the soil is gray, red or black in colour and the place is neither too dry nor too moist; neither it has an abundance of rock particles or sand. The land is fertile sustaining all kinds of trees and crops. Here dosha is generally maintained in a balanced state and is reflected in the Prakrithi of the inhabitants.Prakrithi with reference to climatic elements (Kalanupatini) Seasonal variations of climatic factors such as solar radiation, humidity, temperature, atmospheric pressure, cloud, etc. provides specific environment for gene expression to constitute a particular Prakrithi. Biology tells us that we are what our genes are. But current research on how environment can influence the gene expression has given rise to the new science of Epigenetics. Prenatal research findings demonstrate the influence the environment present in the mother’s womb has on the fetus and the way the child’s mental and physical health get affected for life. ‘Kalagarbhasaya Prakrithi’ – climatic and intra uterine environment have tremendous influence in the expression of genetic material and have influence in the determination of Prakrithi of an individual. Temperature effects the changes in penitrance of genes. The general temperature at which normal phenotypes are produced is referred to as permissive temperature and that which produces mutant phenotypes is called restrictive temperature. Environmental factors such as temperature, light, humidity, radiation etc. appear to have an ability to modify the proteins that act as gates in activating or 31
  32. 32. turning off the genes, thus controlling the gene expression which is reflected in the Prakrithi of the individual.Prakrithi with reference to age factors (Vayonupatini) Age factor has also an important role in the physiological and psychological development of human beings. Age, according to Ayurveda, is a state of body, which depends on the course of time. Human beings have three state of body – age – Baala (childhood, 1-16yrs), Madhya (adolescence, 17-60yrs), Vridha (old age, above 60yrs). The effects of predominance of Kapha, Pitha, and Vatha have most and respective influences in the metabolic state of body during these periods34. Charaka point out that, during childhood, the growth rate of body is comparatively high and the tissues are not fully developed and differentiated. The individual will be tender hearted, easily distressed by mild hurt and insult and is not at all hot tempered with physical and mental dispositions yet to be developed. Softness, complexion, tenderness and unctuousness of the body are in maximum in this period. In adolescence, strength, energy, man hood, bravery etc. reaches its peak; the capacity to receive, preserve and recollect information are maximized and the individual masters the art of communication by speech. The body tissues are fully developed and differentiated in this period and are maintained undisturbed up to the age of 60. Due to dominance of Pitha during this period, the individual is more or less quick tempered and his actions may reflect rebellion against traditions of the society. During senility (old age) degenerative changes occurs in the tissues. Higher mental activities, sensory and motoric potentialities, immunological status, libido and bravery gradually decline. The capacity to receive, preserve and recollect information and 32
  33. 33. communication skills gradually begin to blunt and Vatha shows dominance during the period.Prakrithi with reference to individual developmental traits(Pratyatma niyata) The Prakrithi of an individual can be assessed from the physical, physiological, psychological characteristics of an individual that are determined by germinal mutations (Praakritha doshaja). Any variation to the above characteristics will endanger the very existence of the individual/ organism, as it will influence the metabolic functions of the body as a whole. Mutations occurring in a somatic cell only produce phenotypic changes in the organ to which the mutant cell belong (Vaikritha doshaja). Prakrithi is determined by Praakritha dosha. Hereditary diseases due to defect in Sukla (sperm) or Arthava (ovum) of the parents such as Kushta, Arsas, Prameha, and Kshaya etc. are called Aadi bala pravritha (dushta sukra sonitha bala jata) as put it by Dalhana, the commentator of Susrutha samhitha35. Though the basic body structure, color of the skin etc are defined by the genes at the time of conception (Sukra Sonitha Prakrithi), what we are in our health and personality depend on the environment including our biological relationship in the womb (garbhaasaya Prakrithi) biosocial relationships in the world and how we perceive our own position relative to the world around. Prenatal research36 shows that it is not merely the post-birth environment that influences an individual. The environment within the mother’s womb too has very significant effect on the health and personality of an individual. The coded genetic information accumulated through the millennia of years of evolution is undoubtedly stored in the DNA. What appears to be more significant is the mechanism of gene expression rather than the presence or absence of a specific gene. Whether a particular gene expresses itself or not or 33
  34. 34. how a protein can form through multiple pathways of instructions of several genes isbeing now understood. The view that mutations and recombinations in DNAdetermine the phenotypic traits is getting modified with the emerging science ofEpigenetics. Epigenetics is the study of heritable changes in gene function that occurwithout a change in the DNA sequence. It provides a handle to understand themechanisms in phenotype transmission and development through gene activationand inactivation without necessarily changing the genes. There are critical periodsduring prenatal development when the environment in the womb is more importantthan the genes on the health we enjoy throughout our life. “Chronic maternal stressduring pregnancy – both emotional and physical – can interfere with how the fetusutilizes nutrients and can affect how well or poorly a child functions psychologicallythroughout life.” The mother’s food habits and life style during pregnancy(mathuraahara vihara Prakrithi) have a significant influence on the child’spersonality, health and disease - janmabala pravritha as put it by Susrutha, such asKubjata, Vamana, Jada (with Vathala food) Khalati, Pinga (with Pithala food) SwitraAnd Pandu (with Sleshmala food) by Vagbhata in Ashtanga Hridayam Sareera. Inshort, the normal characters such as stature, facies, colour of eye, type of hair,fertility, vigor, longevity, etc. transmitted from parent to offspring enable to assess thePrakrithi of an individual where as the abnormal characteristics manifested help tounderstand the hereditary disease (Vikrithi).The physical, physiological, psychological characteristics of an individual that arefixed at the time of fertilization (garbhaadi pravritha) by germinal mutations(Praakritha doshaja) that will enable to determine the Prakrithi of an individual istabulated (table no 2) below: 34
  35. 35. 1. General body built and other features.In Vatha Prakrithi In Pitha Prakrithi In Kapha Prakrithi1. Ugly 1. Ugly 1. Beautiful, delightful and lovely.2. Emaciated and lean 2. Body parts weak and 2. Thick feeble3. Rough and rigid 3. Loosen 3. Greasy and tender body body4. Prominent tendons 4. Loosen and delicate 4. Muscular body, smooth musculature musculature5. ---- 5. Whitish or yellow 5. White and yellow complexion complexion6. Net work of vessels 6. ------ 6. ------ prominent7. ------ 7. Joint tender and 7. Joints lubricated and loosen smooth in working2. Body formation.In Vatha Prakrithi In Pitha Prakrithi In Kapha Prakrithi1. Un proportionate and 1. Symmetrical 1. Balanced andasymmetrical. proportionate2. ------- 2. Strong and round body 2. Strong and round body3. ------ 3. Soft and loose 3. Easily movable ligaments ligaments4. ------ 4. ------- 4. Joints, body parts and muscles are well covered or concealed. 35
  36. 36. 3. Skin and Temperature.In Vatha Prakrithi In Pitha Prakrithi In Kapha Prakrithi1. Dry, cracked, wrinkled 1. Early wrinkled, spotted/ 1. Smooth, oily and luster(hands & feet) pimpled/ boils.2. Cold in touch, 2. Warm in touch 2. Low and regulartemperature irregular and temperature.low.3. Intolerable to cold, 3. Intolerable to heat and 3. Tolerable to heat.prefers hot weather. prefers cold.4. ------ 4. Excessive perspiration 4. -------5. ----- 5. ------- 5. Unguent etc. are dried lately6. Body odourless 6. ------ 6. -----4. ColourIn Vatha Prakrithi In Pitha Prakrithi In Kapha Prakrithi1. Black and Dusty 1. White, yellowish, pale 1. Golden yellow, clear red, saffron and pigmented2. ------- 2. White coloured teeth 2. -------5. JointsIn Vatha Prakrithi In Pitha Prakrithi In Kapha Prakrithi1. Swift (rapid) movement 1. Movements are agitated 1. Slow in movementsof joints with a feeling of uneasiness while moving.2. Loose joints 2. Relaxed joints; 2. Strong and steady joints ligaments loose.3. Sound produced in the 3. ------ 3. ------ 36
  37. 37. movements of the joints4. -------- 4. ------ 4. Concealed and symmetrical joints5. -------- 5. -------- 5. Walks steady & firm6. Dietetic preferences.In Vatha Prakrithi In Pitha Prakrithi In Kapha Prakrithi1. Likes diet of sweet, 1. Dislikes acidic 1. Prefers sweets.acidic and saltish tastes. substances.2. Prefers hot (warm) 2. Prefers cold 2. Prefers hot preparationspreparations preparations3. ------- 3. ------- 3. Takes light but maintains strong structure4. Prefers fat rich diet 4. ------- 4. Prefers dry diet and it suits him.7. Food habitsIn Vatha Prakrithi In Pitha Prakrithi In Kapha Prakrithi1. Moderate in diet 1. Excessive diet 1. Very moderate in diet2. Eats swiftly 2. ------- 2. Eats slowly3. Irregular in diet habits 3. Takes edibles many 3. Moderate in taking food. times (frequently)8. DigestionIn Vatha Prakrithi In Pitha Prakrithi In Kapha Prakrithi1. Irregular digestion 1. Quick digestion 1. Weak in digestion2. ------- 2. Intense hunger and 2. --------- thirst 37
  38. 38. 9. BowelIn Vatha Prakrithi In Pitha Prakrithi In Kapha Prakrithi1. Hard bowel 1. Soft bowel 1. Moderate bowel2. Requires strong 2. Requires light 2. Requires mediumpurgatives for removing purgatives purgativesconstipation3. Constipation 3. ------ 3. -------10. Excretion and Perspiration tendencyIn Vatha Prakrithi In Pitha Prakrithi In Kapha Prakrithi1. Less in quantity 1. More in quantity 1. Less in quantity2. ----- 2. Passes urine and 2. -------- excreta in more quantity.11. Physical strengthIn Vatha Prakrithi In Pitha Prakrithi In Kapha Prakrithi1. Physical strength less 1 Moderate strength 1. Strong2. Endurance 2. Low endurance 2. Endurance (Incapable of bearing the troubles)3. ----- 3. Courageous and brave 3. --------4. Gets fatigued early. 4. ------- 4. -------12. SmellIn Vatha Prakrithi In Pitha Prakrithi In Kapha Prakrithi1. ------- 1. Unpleasant, foul and 1. Sweet agar like 38
  39. 39. 13. HairIn Vatha Prakrithi In Pitha Prakrithi In Kapha Prakrithi1. Hard and rough 1. Soft 1. --------14. EyesIn Vatha Prakrithi In Pitha Prakrithi In Kapha Prakrithi1. Dusky 1. Coppery red color 1. Whitish2. Spherical, small in size 2. Rounded 2. Large, broad and elongated3. ------- 3. Eyelashes thin 3. Lashes dense, dark4. Thin lid 4. Thin lid 4. ------5. Unsteady brow 5. ------ 5. -----6. Fluctuating eyeball 6. ------- 6. ----7. Movement of eyelids 7. ------ 7. -----fixed8. Rapid and much 8. ------ 8. ------twinkling of the eye9. Emaciated, unattractive 9. ----- 9. -----10. ------- 10. Feels pleasant in 10. ----- mist and cold15. Lips, Tongue and PalateIn Vatha Prakrithi In Pitha Prakrithi In Kapha Prakrithi1. Unsteady and unsettled 1. Coppery 1. ------- 39
  40. 40. 16. Speech and VoiceIn Vatha Prakrithi In Pitha Prakrithi In Kapha Prakrithi1. Swift in speech 1. Talks rapidly 1. Speaks gently2. Much talkative voice 2. Aggressive 2. Moderate in talk17. Mental StrengthIn Vatha Prakrithi In Pitha Prakrithi In Kapha Prakrithi1. Coward 1. Bold 1. Courageous2. Unstable 2. ------ 2. Steady and firm3. Feeble minded 3. ----- 3. -----4. Agonized with grief 4. ----- 4. -----5. Cherishing to humble 5. Haughty 5. Forgivenesspersons18. Reproductive StrengthIn Vatha Prakrithi In Pitha Prakrithi In Kapha Prakrithi1. Less children 1. Less children 1. More children2. Un-liked by women 2. Un-liked by women 2. Liked by women3. ------ 3. Less inclined in sex 3. More inclined in sex4. ---- 4. Sperm quantity less 4. Profuse quantity of sperm19. Life SpanIn Vatha Prakrithi In Pitha Prakrithi In Kapha Prakrithi1. Less 1. Moderate 1. Long 40
  41. 41. 20. Positions and DignityIn Vatha Prakrithi In Pitha Prakrithi In Kapha Prakrithi1. Finance-poor 1. Moderate finance 1. Rich and wealthy2. Means and luxuries-less 2. Moderate 2. ------3. Fried circle- limited 3. ------ 3. Friendship stable4. ------ 4. Dignified 4. Fortunate, prosperous5. ----- 5. ----- 5. Attendants-abundant21. Provocation of doshasIn Vatha Prakrithi In Pitha Prakrithi In Kapha Prakrithi1. More susceptible to 1. More susceptible to 1. More susceptible toVatha ailments Pitha ailments Kapha ailments22. SleepIn Vatha Prakrithi In Pitha Prakrithi In Kapha Prakrithi1. Sleep less 1. ------- 1. Sleepy and drowsy2. Habit of teeth grinding 2. ----- 2. -----and beating of teeth insleep3. Eyes and mouth remain 3. ------ 3. -----slightly open at sleep4. Sudden sleep walking 4. ----- 4. ------23. DreamsIn Vatha Prakrithi In Pitha Prakrithi In Kapha Prakrithi1. Fearful in dreams 1. ------- 1. ------- 41
  42. 42. 2. Riding on camels, 2. Dreams of gold, 2. Dreams of ponds full ofwalking on hells, climbing palasa, karnikara; lotus, Hans, rows of birds,on trees, flying in sky flames of fire chakravaka, clouds.24. Conduct and PurityIn Vatha Prakrithi In Pitha Prakrithi In Kapha Prakrithi1. ------- 1. Excess and quick in 1. ------ anger2. ----- 2. Excess in envious 2. Less envious3. ----- 3.Pious 3. Good character25. SimiliaIn Vatha Prakrithi In Pitha Prakrithi In Kapha Prakrithi1. Goat, jackal, rabbit, rat, 1. Snake, owl, 1. Brahma, rudra, varuna,camel, dog, vulture, crow gandharva, yaksha, indra, lion, horse, elephant, monkey, tiger, bear, cow, ox, leopard, swan. mongoose(Courtesy: Psycho- Pathology in Indian medicine) 42
  43. 43. GENESA bird’s eye - view on genetics is essential before review of literature of the genesincluded in my present study.Gene is the fundamental physical and functional unit of heredity, which carriesinformation from one generation to the next. Genes make proteins. Proteins makecells carry out the various functions of the body. Proteins are made of 20 buildingblocks of life called amino acids. They combine in a thousand different ways to makevarious types of proteins. Billions of proteins combine to make a cell; billions of cellscombine to make a tissue; thousands of tissues combine to make an organ, andseveral organs, to make a man1.Life begins with a single cell. By adulthood the single cell will have replicated, dividedand differentiated many times to make a three trillion-cell human being. Each cellcontains about 30000 genes and their collective interactions in our body give us life.The normal functioning of genes keeps us healthy. When genes are exposed toharmful environments, they alter their functions. It is called mutation. Mutations arechemical imperfections in this process, where a base is accidentally skipped,inserted, or incorrectly copied, or the chain is trimmed, or added to; many basicmutations can be described as combinations of these accidental "operations".Mutations can also occur through chemical damage (through mutagens), light (UVdamage), or through other more complicated gene swapping events. A mutatedgene makes a wrong protein and this is what makes us sick. Hence all diseaseshave a genetic origin.There are also millions of plants on earth. Many of them have developed toxins toprotect themselves against insects and environment. Those plants that producedtoxins were able to survive. These toxins act as active molecules in and have the 43
  44. 44. unique ability to bind to human genes too and are able to switch a gene on or off. Ifthe switching on and off of a gene is desirable, it will lead to cure of disease whengenes are switched on it produces a protein. Once produced, the protein interactswith the many other proteins in the cell, according to the cell metabolism. Thisinteraction finally produces the trait. The protein floats around in our blood streamuntil it comes in contact with a receptor site. If the protein is a bad one made by amutated gene, it can produce a disease or its simply floats around for a while andfinally is filtered out of the body.Genes are encoded in an organisms genome, composed of DNA or RNA, and directthe physical development and behavior of the organism. Most genes encodeproteins, which are biological macromolecules comprising linear chains of aminoacids that effect most of the chemical reactions carried out by the cell. Some genesdo not encode proteins, but produce non-coding RNA molecules that play key rolesin protein biosynthesis and gene regulation. Molecules that result from geneexpression, whether RNA or protein, are collectively known as gene products.Most genes contain non-coding regions, that do not code for the gene products, butoften dictate gene regulation. A critical non-coding region is the promoter, a shortDNA sequence that is required for initiation of gene expression. The genes ofeukaryotic organisms often contain non-coding regions called introns which areremoved from the messenger RNA in a process known as splicing. The regions thatactually encode the gene product, which can be much smaller than the introns, areknown as exons.The word "gene" was coined in 1909 by Danish botanist Wilhelm Johannsen for thefundamental physical and functional unit of heredity. The word was derived fromHugo De Vries term pangen, itself a derivative of the word pangenesis coined by 44
  45. 45. Darwin (1868). The word pangenesis is made from the Greek words pan (a prefixmeaning "whole", "encompassing") and genesis ("birth") or genos ("origin").Although classical genetics and evolutionary biology use the term "gene" to refer to aconceptual entity or "unit of inheritance", modern molecular genetics typically usesthe term to refer to a physical molecule. Gene Ontology system, defines a gene as "alocatable region of genomic sequence, corresponding to a unit of inheritance, whichis associated with regulatory regions, transcribed regions and/or other functionalsequence regions".The word "gene" is also used in common speech to refer to the inheritance of a trait,as in "a cancer gene" or "the gene for obesity"; however, biologists rarely use theterm in this sense because it is highly unlikely that such complex and large-scalephenomena would be attributable to the influence of a single molecular gene.In molecular biology, a gene is a region of DNA (or RNA, in the case of someviruses) that determines the amino acid sequence of a protein (the coding sequence)and the surrounding sequence that controls when and where the protein will beproduced (the regulatory sequence). The genetic code determines how the codingsequence is converted into a protein sequence. The protein-coding regions of genesare composed of a series of three-nucleotide sequences called codons. Each codonspecifies a particular amino acid to be added to the protein chain; thus genesdetermine the proteins primary structure. Most genes are expressed in a two-stageprocess: first, the DNA is transcribed by enzymes known as RNA polymerases toproduce an RNA molecule known as messenger RNA (mRNA), and second, themRNA is translated by specialized cellular machinery known as the ribosome into apolypeptide chain that then folds into a functional protein. The genetic code isessentially the same for all known life, from bacteria to humans. 45
  46. 46. Through the proteins they encode, genes govern the cells in which they reside. Inmulticellular organisms, they control the development of the individual from thefertilized egg and the day-to-day functions of the cells that make up tissues andorgans. The roles of their protein products range from mechanical support of the cellstructure to the transportation and manufacture of other molecules and to theregulation of other proteins activities.Due to rare, spontaneous errors (e.g. in DNA replication), mutations in the sequenceof a gene may arise. Once propagated to the next generation, this mutation may leadto variations within a species population. Variants of a single gene are known asalleles, and differences in alleles may give rise to differences in traits, for exampleeye colour. A genes most common allele is called the wild type allele, and rarealleles are called mutants.All the genes and intervening DNA together make up the genome of an organism,which in many species is divided among several chromosomes and typically presentin two or more copies. The location (or locus) of a gene and the chromosome onwhich it is situated is in a sense arbitrary. Genes that appear together on thechromosomes of one species, such as humans, may appear on separatechromosomes in another species, such as mice. Two genes positioned near oneanother on a chromosome may encode proteins that figure in the same cellularprocess or in completely unrelated processes. As an example of the former, many ofthe genes involved in spermatogenesis reside together on the Y chromosome.Many species carry more than one copy of their genome within each of their somaticcells. These organisms are called diploid if they have two copies or polyploid if theyhave more than two copies. In such organisms, the copies are practically neveridentical. With respect to each gene, the copies that an individual possesses are 46
  47. 47. liable to be distinct alleles, which may act synergistically or antagonistically togenerate a trait or phenotype. The ways that gene copies interact are explained bychemical dominance relationshipsThe existence of genes was first suggested by Gregor Mendel, who, in the 1860s,studied inheritance in pea plants and hypothesized a factor that conveys traits fromparent to offspring. Although he did not use the term gene, he explained his resultsin terms of inherited characteristics. Mendel was also the first to hypothesizeindependent assortment, the distinction between dominant (An allele that determinesphenotype even when heterozygous. Also the trait controlled by that allele) andrecessive (a gene that is phenotypically manifest in the homozygous state but ismasked in the presence of a dominant allele) traits, the distinction between aheterozygote (A diploid or polyploid with different alleles at a particular locus) andhomozygote (A diploid or polyploid with identical alleles at a particular locus), and thedifference between what would later be described as genotype and phenotype.Mendels concept was finally named when Wilhelm Johannsen coined the word genein 1909.In the early 1900s, Mendels work received renewed attention from scientists. In1910, Thomas Hunt Morgan showed that genes reside on specific chromosomes. Helater showed that genes occupy specific locations on the chromosome. With thisknowledge, Morgan and his students began the first chromosomal map of the fruit flyDrosophila. In 1928, Frederick Griffith showed that genes could be transferred. Inwhat is now known as Griffiths experiment, injections into a mouse of a deadly strainof bacteria that had been heat-killed transferred genetic information to a safe strainof the same bacteria, killing the mouse. 47
  48. 48. In 1941, George Wells Beadle and Edward Lawrie Tatum showed that mutations ingenes caused errors in certain steps in metabolic pathways. This showed thatspecific genes code for specific proteins, leading to the "one gene, one enzyme"hypothesis. Oswald Avery, Collin Macleod, and Maclyn McCarty showed in 1944 thatDNA holds the genes information. In 1953, James D. Watson and Francis Crickdemonstrated the molecular structure of DNA. Together, these discoveriesestablished the central dogma of molecular biology, which states that proteins aretranslated from RNA which is transcribed from DNA. This dogma has since beenshown to have exceptions, such as reverse transcription in retroviruses.Richard Roberts and Phillip Sarp discovered in 1977 that genes can be split intosegments. This leads to the idea that one gene can make several proteins. Recently(as of 2003-2006), biological results let the notion of gene appear more slippery. Inparticular, genes do not seem to sit side by side on DNA like discrete beads. Instead,regions of the DNA producing distinct proteins may overlap, so that the ideaemerges that "genes are one long continuum". (Pearson, 2006)Genes under studyMolecular typing of the following genes was carried out using the polymerase chainreaction in the present study.1. Dopamine Receptor D2 Taq 1 D DRD2 Taq 1 D2. Dopamine Receptor D2 Taq 1 B DRD2 Taq 1 B3. Dopamine Receptor D2 Taq 1 A DRD2 Taq 1 A4. Dopamine Receptor D2 Serine 311 Cysteine DRD2 S311C5. Dopamine Receptor D2 Histidine 313 H DRD2 His 313H6. Dopamine Receptor D3 Serine 9Glycine DRD3 S9G 48
  49. 49. 7. 5-Hydroxy Tryptamine Receptor 1 B 5HTR 1B8. Serotonin 1438 Ser 14389. Serotonin 102 Ser 10210. Human Leukocyte Antigen B HLA B11. Human Leukocyte Antigen A HLA ADopamine Receptor D2 Taq 1D, Taq 1B, Taq 1AHuman dopaminergic neurons are involved in the control of hormone secretion,voluntary movement, and emotional behavior. Mediating these effects are thedopamine D1 and D2 receptors. These macromolecules belong to a large family ofrelated sequences known as the G protein-coupled receptors. The D2 receptorshave been of special interest because they bind, with high affinity and specificity,many of the commonly prescribed antipsychotic drugs.1. Taq 1DKidd, Kenneth K. in a study of "A global survey of haplotype frequencies and linkagedisquilibrium at the DRD2 locus." Reported in Human Genetics Aug., 1998; 103 (2)211-227, is the only reference that I could get about Taq 1D. He has reported thatthe coding region of DRD2 gene contains four RSPs (restriction site polymorphisms),Taq1A, Taq1B, and Taq1D. It also includes a one-dinucleotide STRP or shorttandem repeat polymorphism. DRD2, coded for by locus 11q23 in the humanchromosome, is one receptor for the neurotransmitter dopamine. Thistransmembrane receptor is a member of the rhodopsin family2. As researchmaterials regarding the study of DRD2 Taq 1D is very rare, I have included it in mypresent study. 49
  50. 50. 2. Taq 1 BA B polymorphism at the CETP (cholesteryl ester protein transfer) locus that isdetectable with the restriction enzyme TaqI is a genetic determinant of the plasmaHDL cholesterol concentration. Cholestery ester transfer protein (CETP) transferscholesteryl esters between lipoproteins. CETP may effect susceptibility toatherosclerosis3.3. Taq 1 AThe catecholamine dopamine, a precursor of noradrenaline and adrenaline, is anendogenous neurotransmitter, which modulates a wide variety of physiologicfunctions including behavior, ion transport, vascular tone, and blood pressure. Thereare reports of a deficiency in renal dopamine synthesis and/or secretion in variousforms of human hypertension. As endogenous renal dopamine plays an importantrole in maintaining body sodium homeostasis, renal dopaminergic deficiency maycontribute to the development and maintenance of high blood pressure, at least in aproportion of subjects with essential hypertension Suppression of dopaminergicactivity has been observed in young normotensive subjects with a family history ofhypertension before the development of hypertension emerged. Dopamine alsoplays a major role in the regulation of appetite. Dopaminergic agonist drugs, such asdextroamphetamine, have been shown to suppress appetite and subsequently toreduce weight, whereas a major side effect of dopamine D2 receptor (DRD2)antagonists, such as haloperidol, is marked weight gain. The dopaminergic systeminvolves the interaction of dopamine with several specific dopamine receptors, whichbelong to a large family of G-protein-coupled receptors. Biochemical andpharmacological studies have shown that the physiological actions of dopamine aremediated by interaction with two basic types of G-protein-coupled receptors, D1-like 50
  51. 51. and D2-like, which stimulate and inhibit, respectively, the enzyme adenyl cyclase.The human DD2R gene contains eight exons, spans at least 50 kilobases (kb), andhas the unusual feature of a large (greater than 25 kb) intron (intron 1) separatingthe presumed promoter region from the protein-coding region. The D2 receptor locushas been localised to the 11q22 to 11q23 region of the human genome. . Previousstudies showed that the allelic variants of the DD2R gene play a role in theregulation of body weight. A genome wide scan provided strong evidence onchromosome 11q of a locus influencing susceptibility to obesity. It has been reportedthat 1A polymorphism to be associated with both obesity and blood pressure innormoglycaemic subjects, but in diabetics only the relationship with obesity wasevident4.4. Dopamine Receptor D2 Serine 311 CysteineDRD2 gene has been suggested to be one missense nucleotide mutation from C toG resulting in a substitution of serine with cystein at the codon 311 located in thethird intracellular loop of the DRD2. Variants of the DRD2 S311C play a major role inconferring susceptibility to major psychoses, connected with disorganized anddelusional symptomatology. The schizophrenics with Cys311 tended to have a lowerage of onset and a positive family history of schizophrenia5.5. Dopamine Receptor D2 Histidine 313 HDysfunction of the dopamine D2 receptor signaling has been associated with theillness, schizophrenia. This study investigates the association of synonymouspolymorphisms (His313 and Pro319) in the dopamine D2 receptor gene may beassociated with schizophrenia. The results demonstrated that genotype distributionfor the His313 polymorphism was significantly different between schizophreniapatients and control subjects6. 51