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Personalized medicine: A near future or yet miles to go?
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AIMED-62; No. of Pages 2 Advances in Integrative Medicine xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Advances in Integrative Medicine journal homepage: www.elsevier.com/locate/aimed
Comments and Commentaries
Personalized medicine: A near future or yet miles to go? Ab Latif Wani Section of Genetics, Department of Zoology, Faculty of Life Science, Aligarh Muslim University, Aligarh 202002, Utter Pradesh, India
A R T I C L E I N F O
Article history: Received 21 February 2015 Received in revised form 27 February 2015 Accepted 26 June 2015 Keywords: Personalized medicine Pharmacogenetics Pharmacogenomic
The development of therapeutics based on pharmacogenetic and pharmacogenomic information which is specific to the individual is called ‘‘personalized medicine’’. The effectiveness of pharmaceutical medicines for different individuals is greatly variable and the outcome of this variable effect of drugs has troubled researchers for decades. Recent data available on the architecture of the human genome explicitly shows that there are large number variations at the genetic level between individuals which accounts for the differences in drug absorption, distribution, metabolism and excretion (ADME) profiles and ultimately the response towards the pharmacological agents [1,2]. Thus, pharmaceutical medicines are usually good for some but not for all patients. Besides genetics, this may partly be due to the differences in personal lifestyles, including diet, habits, occupation, etc. A major reason for such discrepancies is the fact that all our common diseases tend to have several different causative agents [3]. Researchers involved in pharmacogenomics expect that advancements in this field will improve our chances to choose the right drug for the patient by categorizing them into genetically definable classes which show similar effects exerted by medications. [4]. With pharmacogenomic analyses we will better be able to identify the genes which are more susceptible to disease and this will also help us in developing potential targeted drugs [5]. This makes the promises of personalized medicine alive leading researchers to explore novel approaches in drug discovery which
E-mail address: [email protected].
include the applications of individualized drug therapy with new insights to prevention of disease. On January 30th 2015, the United States President, Barack Obama, unveiled the ‘‘Precision Medicine Initiative (PMI)’’ which will account for US$ 215 million in his budget proposal [6]. The aim of this initiative will be to gather personalized information which will help in the development of personalized medicine. However, with human genomic information exploration and its availability with the increasing pace of genomic research, the original objective of developing personalized medicine seems to be drifting away. Recent research sheds light on this, in which researchers have found a large number of genetic variants which are very specific to each individual [7]. In the same study, researchers analyzed the genetic makeup of several hundred people in order to decode the genetic information on two sets of chromosomes separately. The results were surprising as the researchers discovered millions of different gene forms from the small group of individuals. Their results also showed that mutations are not random, but are distributed in the same ratio in every individual which includes two sets of chromosomes from parents. The mutations were found to occur with an average cis/trans ratio of 60:40, that is, 60% of the mutations affect the same chromosomes sets and 40% affects both sets of chromosomes. The first human genome was sequenced in 2001. From that time, scientists were hoping to develop treatment drugs based on the information of every single gene. However, with the growing pace of human genome research, amazing findings are continually listed day after day. With the development of more recent techniques like molecular genetics and bioinformatic methods, the sequencing of genes from two sets of human chromosomes separately has become easier. In the aforementioned study,
http://dx.doi.org/10.1016/j.aimed.2015.06.001 2212-9588/ß 2015 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Wani AL. Personalized medicine: A near future or yet miles to go? Adv Integr Med (2015), http:// dx.doi.org/10.1016/j.aimed.2015.06.001
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AIMED-62; No. of Pages 2 2
A.L. Wani / Advances in Integrative Medicine xxx (2015) xxx–xxx
researchers decoded the maternal and paternal genes from a set of 14 genomes and supplemented their analysis with the genetic information of 372 Europeans for the ‘‘1000 Genomes Project’’ [7]. Their results showed that most of the genes of the population occur in different forms. They further estimated that about 250 gene variants of each gene can exist. Approximately four million different gene forms were found from the analysis of 400 genomes which rises with an increase in the number of genomes analyzed. It has been observed that more than 85% of genes do not exist in any predominant form in more than half of all individuals. Thus, such an enormous diversity of gene forms means that over half of these genes exist in their unique form in every individual which makes them especially personalized. This challenges the traditional and overly simplistic view about genes that there is one wild or predominant form and few recessive or mutant forms which is widely misleading [8]. It is perceived therefore that the present view about genes and gene mutations is no longer adequate. With such a changing scenario about genetic mutations, it is now speculated that scientists will have to examine the two paternal genes separately which includes measuring the effect of the interaction which they share in the form of a pair. The genes which occur in different forms of variants also have an effect at the protein level. This subsequently leads to different responses from using different types of drugs among individuals. These genes play an important role in controlling the signalling transduction between the cells, immune system and also gene activity. Due to having a large number of variants, the body has the efficient capacity of using the selected or more favourable variants in order to adapt to changes in the processes of the body in itself and of the environment. However, if the duality of the proteins balances in an uneven manner, this may in fact cause a pathogenic condition or predispose some individuals to a lowered immune system by making the wrong protein. The researchers in the study [7] discovered that 96% of all the genes have at least 5–20 different protein forms, implying that 20 different proteins can be coded by single gene. This makes the personalized medicine initiative even more complex as scientists
now have to know which protein form is present at the individual level before taking any move towards treatment with personalized medicine. Such a diversity of protein and gene variants among individuals results in tremendous differences. With such research reports and the changing interpretation of genetic analysis, there may be a major shift in the understanding about how to predict disease in the population. The information gathered about human genomic research from the past decades had put forward the daunting task for drug development in the form of personalized medicine. Though it can be hoped that the days are not too far when personalized medicine becomes available, the current available data about human genomic research suggests that we have many miles to go before we can confidently make an affirmation about the development of personalized medicine. Conflict of interest Nil. Funding Nil. References [1] M.R. Meyer, H.H. Maurer, Absorption, distribution, metabolism and excretion pharmacogenomics of drugs of abuse, Pharmacogenomics 12 (2011) 215–233. [2] Q. Ma, A.Y. Lu, Pharmacogenetics, pharmacogenomics, and individualized medicine, Pharmacol. Rev. 63 (2011) 437–459. [3] R.A. King, J.I. Rotter, A.G. Motulsky, The Genetic Basis of Common Diseases, Oxford University Press, Minneapolis, 2001. [4] W. Kalow, Pharmacogenetics and personalised medicine, Fundam. Clin. Pharmacol. 16 (2002) 337–342. [5] L. Mancinelli, M. Cronin, W. Sade´e, Pharmacogenomics: the promise of personalized medicine, AAPS PharmSci. 2 (1) (2000) E4. [6] http://www.personalizedmedicinecoalition.org (retrieved on 21.02.15). [7] M.R. Hoehe, G.M. Church, H. Lehrach, T. Kroslak, S. Palczewski, K. Nowick, S. Schulz, E.K. Suk, T. Huebsch, Multiple haplotype-resolved genomes reveal population patterns of gene and protein diplotypes, Nat. Commun. 5 (2014) 5569, http://dx.doi.org/10.1038/ncomms6569. [8] J.C. Stephens, et al., Haplotype variation and linkage disequilibrium in 313 human genes, Science 293 (2001) 489–493.
Please cite this article in press as: Wani AL. Personalized medicine: A near future or yet miles to go? Adv Integr Med (2015), http:// dx.doi.org/10.1016/j.aimed.2015.06.001
AIMED-62; No. of Pages 2 Advances in Integrative Medicine xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Advances in Integrative Medicine journal homepage: www.elsevier.com/locate/aimed
Comments and Commentaries
Personalized medicine: A near future or yet miles to go? Ab Latif Wani Section of Genetics, Department of Zoology, Faculty of Life Science, Aligarh Muslim University, Aligarh 202002, Utter Pradesh, India
A R T I C L E I N F O
Article history: Received 21 February 2015 Received in revised form 27 February 2015 Accepted 26 June 2015 Keywords: Personalized medicine Pharmacogenetics Pharmacogenomic
The development of therapeutics based on pharmacogenetic and pharmacogenomic information which is specific to the individual is called ‘‘personalized medicine’’. The effectiveness of pharmaceutical medicines for different individuals is greatly variable and the outcome of this variable effect of drugs has troubled researchers for decades. Recent data available on the architecture of the human genome explicitly shows that there are large number variations at the genetic level between individuals which accounts for the differences in drug absorption, distribution, metabolism and excretion (ADME) profiles and ultimately the response towards the pharmacological agents [1,2]. Thus, pharmaceutical medicines are usually good for some but not for all patients. Besides genetics, this may partly be due to the differences in personal lifestyles, including diet, habits, occupation, etc. A major reason for such discrepancies is the fact that all our common diseases tend to have several different causative agents [3]. Researchers involved in pharmacogenomics expect that advancements in this field will improve our chances to choose the right drug for the patient by categorizing them into genetically definable classes which show similar effects exerted by medications. [4]. With pharmacogenomic analyses we will better be able to identify the genes which are more susceptible to disease and this will also help us in developing potential targeted drugs [5]. This makes the promises of personalized medicine alive leading researchers to explore novel approaches in drug discovery which
E-mail address: [email protected].
include the applications of individualized drug therapy with new insights to prevention of disease. On January 30th 2015, the United States President, Barack Obama, unveiled the ‘‘Precision Medicine Initiative (PMI)’’ which will account for US$ 215 million in his budget proposal [6]. The aim of this initiative will be to gather personalized information which will help in the development of personalized medicine. However, with human genomic information exploration and its availability with the increasing pace of genomic research, the original objective of developing personalized medicine seems to be drifting away. Recent research sheds light on this, in which researchers have found a large number of genetic variants which are very specific to each individual [7]. In the same study, researchers analyzed the genetic makeup of several hundred people in order to decode the genetic information on two sets of chromosomes separately. The results were surprising as the researchers discovered millions of different gene forms from the small group of individuals. Their results also showed that mutations are not random, but are distributed in the same ratio in every individual which includes two sets of chromosomes from parents. The mutations were found to occur with an average cis/trans ratio of 60:40, that is, 60% of the mutations affect the same chromosomes sets and 40% affects both sets of chromosomes. The first human genome was sequenced in 2001. From that time, scientists were hoping to develop treatment drugs based on the information of every single gene. However, with the growing pace of human genome research, amazing findings are continually listed day after day. With the development of more recent techniques like molecular genetics and bioinformatic methods, the sequencing of genes from two sets of human chromosomes separately has become easier. In the aforementioned study,
http://dx.doi.org/10.1016/j.aimed.2015.06.001 2212-9588/ß 2015 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Wani AL. Personalized medicine: A near future or yet miles to go? Adv Integr Med (2015), http:// dx.doi.org/10.1016/j.aimed.2015.06.001
G Model
AIMED-62; No. of Pages 2 2
A.L. Wani / Advances in Integrative Medicine xxx (2015) xxx–xxx
researchers decoded the maternal and paternal genes from a set of 14 genomes and supplemented their analysis with the genetic information of 372 Europeans for the ‘‘1000 Genomes Project’’ [7]. Their results showed that most of the genes of the population occur in different forms. They further estimated that about 250 gene variants of each gene can exist. Approximately four million different gene forms were found from the analysis of 400 genomes which rises with an increase in the number of genomes analyzed. It has been observed that more than 85% of genes do not exist in any predominant form in more than half of all individuals. Thus, such an enormous diversity of gene forms means that over half of these genes exist in their unique form in every individual which makes them especially personalized. This challenges the traditional and overly simplistic view about genes that there is one wild or predominant form and few recessive or mutant forms which is widely misleading [8]. It is perceived therefore that the present view about genes and gene mutations is no longer adequate. With such a changing scenario about genetic mutations, it is now speculated that scientists will have to examine the two paternal genes separately which includes measuring the effect of the interaction which they share in the form of a pair. The genes which occur in different forms of variants also have an effect at the protein level. This subsequently leads to different responses from using different types of drugs among individuals. These genes play an important role in controlling the signalling transduction between the cells, immune system and also gene activity. Due to having a large number of variants, the body has the efficient capacity of using the selected or more favourable variants in order to adapt to changes in the processes of the body in itself and of the environment. However, if the duality of the proteins balances in an uneven manner, this may in fact cause a pathogenic condition or predispose some individuals to a lowered immune system by making the wrong protein. The researchers in the study [7] discovered that 96% of all the genes have at least 5–20 different protein forms, implying that 20 different proteins can be coded by single gene. This makes the personalized medicine initiative even more complex as scientists
now have to know which protein form is present at the individual level before taking any move towards treatment with personalized medicine. Such a diversity of protein and gene variants among individuals results in tremendous differences. With such research reports and the changing interpretation of genetic analysis, there may be a major shift in the understanding about how to predict disease in the population. The information gathered about human genomic research from the past decades had put forward the daunting task for drug development in the form of personalized medicine. Though it can be hoped that the days are not too far when personalized medicine becomes available, the current available data about human genomic research suggests that we have many miles to go before we can confidently make an affirmation about the development of personalized medicine. Conflict of interest Nil. Funding Nil. References [1] M.R. Meyer, H.H. Maurer, Absorption, distribution, metabolism and excretion pharmacogenomics of drugs of abuse, Pharmacogenomics 12 (2011) 215–233. [2] Q. Ma, A.Y. Lu, Pharmacogenetics, pharmacogenomics, and individualized medicine, Pharmacol. Rev. 63 (2011) 437–459. [3] R.A. King, J.I. Rotter, A.G. Motulsky, The Genetic Basis of Common Diseases, Oxford University Press, Minneapolis, 2001. [4] W. Kalow, Pharmacogenetics and personalised medicine, Fundam. Clin. Pharmacol. 16 (2002) 337–342. [5] L. Mancinelli, M. Cronin, W. Sade´e, Pharmacogenomics: the promise of personalized medicine, AAPS PharmSci. 2 (1) (2000) E4. [6] http://www.personalizedmedicinecoalition.org (retrieved on 21.02.15). [7] M.R. Hoehe, G.M. Church, H. Lehrach, T. Kroslak, S. Palczewski, K. Nowick, S. Schulz, E.K. Suk, T. Huebsch, Multiple haplotype-resolved genomes reveal population patterns of gene and protein diplotypes, Nat. Commun. 5 (2014) 5569, http://dx.doi.org/10.1038/ncomms6569. [8] J.C. Stephens, et al., Haplotype variation and linkage disequilibrium in 313 human genes, Science 293 (2001) 489–493.
Please cite this article in press as: Wani AL. Personalized medicine: A near future or yet miles to go? Adv Integr Med (2015), http:// dx.doi.org/10.1016/j.aimed.2015.06.001