India is a conglomerate of multitude of languages, ethnicities, castes, tribes and religions. While language and ethnicity are geographical divisions, caste and religion are socio-cultural divisions. The origin and diversity of population of India has been the subject of speculation for long.
The major present day view is based on the ‘Aryan invasions hypotheses’, postulated during late 19th century, which suggest the migration of Aryans from west Asia or Europe to northern India. These hypotheses, based mainly on linguistic studies, suggest the arrival of Aryans towards the end of Indus valley civilization at about 1800 BCE. There are also opposing views, though not favorite, that the focus was India and migrated to the west.
Researchers from Center for Cellular and Molecular Biology in Hybrabad, India along with collaborators at Harvard University have published a population genetics study on Indian population this week in journal Nature (September 23, 2009). Population genetics is the study of allele frequency and changes under the influence of various evolutionary pressures. They analyzed thousands of DNA variations from the genome of 132 individuals belonging to many ethnic groups from India to come to their conclusions. They draw compelling evidence about 2 major founder populations which makes up most of the present day Indians, who are a mixture of these now. An Ancestral South Indian group, found only in India, and an Ancestral North Indian group distantly related to west Asian and European populations.
Does the current finding that the Ancestral North Indian founder population is related to west Asians support any of these hypotheses? Probably not, the Aryan invasion is estimated at about 1800 BC, while the age of Ancestral North Indian founder population is tens of thousands of years older. Like the present day Indians, the people at the time of Indus valley civilization may already have a mixed genetics of both North Indian and South Indian founder population. In fact, none of the recent genetics studies support an Aryan Genetics trait for this period.
Anthropogenesis, or study of human evolution, have put modern human to have evolved about 100,000 years ago. The ‘out of Africa’ hypothesis assume human to have originated in Africa and spread across the world. While an alternate multiregional hypothesis argue geographically distinct but interbreeding parallel evolution of humans. Is the Ancestral South Indian founder population, which probably much older than the Ancestral North Indian founder population, came from Africa or evolved in South Asia?
Some of the more recent genetics studies on mitochondrial DNA and Y chromosome variations also do not support an Aryan invasion theory. Genetic studies including more ethnic groups and larger population samples are needed to paint a better picture of human evolution and migration patterns in India and South Asia.
September 27, 2009
September 23, 2009
The Age of Biotherapeutics
This article is partly based on my previous publication in the journal BioSpectrum titled “Serum free media - All are not created equal” August 2008 (http://www.biospectrumasia.com/content/130808ind6802.asp).
During the last century we saw major advances in controlling infectious diseases by way of vaccination as well as development of antibiotics. We also saw hundred of small chemical molecular drugs developed for various indications. Until then infectious diseases were the major killer around the world. There were many recorded incidences of Pandemic, the Black Death for example, during middle-ages probably wiped out over 50% percent of population of Europe. With the advances in medicine during the last century, the life expectancy have gone up significantly especially in the developed countries.
As the median age of the population went up, the patterns of diseases have changed. Now cardiovascular and metabolic diseases, such as diabetes and obesity, are major causes of morbidity and mortality. Also many geriatric conditions, such as Alzheimer’s disease and dementia, are becoming more prevalent.
In this century we will see developments in biotherapeutics and personalized medicine to combat these ailments. By biotherapeutics I mean drugs of biological origin such as recombinant proteins and antibodies. The pharmaceutical industry went through a major paradigm change in their product development strategy during the last decade. Until recently they were very much focused on small molecule based drug development. Things started changing over last 10 years or so when more and more protein based drugs got approvals and some became blockbuster drugs. Probably the success of Rituxan/MabThera, for the treatment of Non Hodgkins lymphoma launched in 1997 by Idec Pharmaceuticals and Genentech, initiated this shift towards biologics or biotherapeutics. Currently, monoclonal antibody development is the fastest growing segment in biotech industry recording 14% annual growth rate (versus 0.6% for small molecule), with recent recorded sales in excess of $20 billion. Over 50% of products in development are biotherapeutics that include monoclonal antibodies and recombinant proteins.
The manufacture of biotherapeutics requires live cells such as bacterial culture, yeast or mammalian cell culture. Many recombinant proteins and antibodies require mammalian cell culture for production. Cells are grown in vitro for the production of proteins they produce including antibodies. About half of all recombinant therapeutic proteins currently in the market are produced in mammalian cells. The accelerated demand of biologics also put lot of demand on bioprocessing to increase capacity, improve on efficiency and yield. Significant progress has been made in in vitro cell culture technologies during last few years. Initial commercial uses of cell culture were for the production of vaccines, such as polio vaccines.
The rapid advancement in development of biopharmaceuticals and biologics recently has forced the industry to come up better solutions to its problems and issues. Major issues are 1) safety associated with use of animal products, 2) consistency of production associated with variability from lot to lot and 3) cost. Cost of manufacturing by mammalian cell culture is high and hence the high cost of many biologics in the market currently. A small improvement in productivity of a cell line may have a significant savings in terms of cost. Currently there are 26 approved monoclonal antibodies in the market some of which can be life saving to many patients. But high cost may be keeping it from the reach of many. The challenge to the industry is to bring the cost down to be affordable to all.
During the last century we saw major advances in controlling infectious diseases by way of vaccination as well as development of antibiotics. We also saw hundred of small chemical molecular drugs developed for various indications. Until then infectious diseases were the major killer around the world. There were many recorded incidences of Pandemic, the Black Death for example, during middle-ages probably wiped out over 50% percent of population of Europe. With the advances in medicine during the last century, the life expectancy have gone up significantly especially in the developed countries.
As the median age of the population went up, the patterns of diseases have changed. Now cardiovascular and metabolic diseases, such as diabetes and obesity, are major causes of morbidity and mortality. Also many geriatric conditions, such as Alzheimer’s disease and dementia, are becoming more prevalent.
In this century we will see developments in biotherapeutics and personalized medicine to combat these ailments. By biotherapeutics I mean drugs of biological origin such as recombinant proteins and antibodies. The pharmaceutical industry went through a major paradigm change in their product development strategy during the last decade. Until recently they were very much focused on small molecule based drug development. Things started changing over last 10 years or so when more and more protein based drugs got approvals and some became blockbuster drugs. Probably the success of Rituxan/MabThera, for the treatment of Non Hodgkins lymphoma launched in 1997 by Idec Pharmaceuticals and Genentech, initiated this shift towards biologics or biotherapeutics. Currently, monoclonal antibody development is the fastest growing segment in biotech industry recording 14% annual growth rate (versus 0.6% for small molecule), with recent recorded sales in excess of $20 billion. Over 50% of products in development are biotherapeutics that include monoclonal antibodies and recombinant proteins.
The manufacture of biotherapeutics requires live cells such as bacterial culture, yeast or mammalian cell culture. Many recombinant proteins and antibodies require mammalian cell culture for production. Cells are grown in vitro for the production of proteins they produce including antibodies. About half of all recombinant therapeutic proteins currently in the market are produced in mammalian cells. The accelerated demand of biologics also put lot of demand on bioprocessing to increase capacity, improve on efficiency and yield. Significant progress has been made in in vitro cell culture technologies during last few years. Initial commercial uses of cell culture were for the production of vaccines, such as polio vaccines.
The rapid advancement in development of biopharmaceuticals and biologics recently has forced the industry to come up better solutions to its problems and issues. Major issues are 1) safety associated with use of animal products, 2) consistency of production associated with variability from lot to lot and 3) cost. Cost of manufacturing by mammalian cell culture is high and hence the high cost of many biologics in the market currently. A small improvement in productivity of a cell line may have a significant savings in terms of cost. Currently there are 26 approved monoclonal antibodies in the market some of which can be life saving to many patients. But high cost may be keeping it from the reach of many. The challenge to the industry is to bring the cost down to be affordable to all.
September 04, 2009
The Genomics of Creation
A basis for generation of diversity of life on earth was first explained by Charles Darwin in his eminent work on evolution ‘The Origin of Species’ in late 19th century. A genetic mechanism for natural selection and speciation was later developed by mutation theory popularized by Theodosius Dobzhansky and others. The gene-centric view of evolution emerged in 1960’s with the discovery of DNA/RNA as the genetic material of all life on earth.
We cannot prove or disprove how life originated on earth, with our current understanding of scientific materialism. Was it formed de novo spontaneously from the crucible of evolution of earth? Was it planted by some asteroids carrying microbes from a distant galaxy? Or is there some cosmic intelligence?
Synthetic biology, the creation of new or alternate forms of life by genetic engineering, has taken off since 1971 when Ananda Chakraborty first created an oil eating bacteria. But so far, no one has not been able to create self replicating organism completely from scratch.
Recently, researchers at the not-for-profit J Craig Venter Institute in Rockville, Maryland, USA have identified a set of minimum genes essential for independent existence and replication of an organism. These fewest possible gene set which allows an organism to grow, replicate and multiply independently was identified by chemical knockout studies of the simplest microbes in existence, Mycoplasma genitalium, which causes urinary tract infections in humans. This knowledge will allow synthetic biologists to create living organisms almost from scratch, and may help to understand molecular mechanisms fundamental to life.
While creation of a simple life form, able to do specific defined functions or self replication may be achievable, creating a sentient being is altogether a different matter. What is soul and consciousness? At what stage of its development does a sentient being get its soul or consciousness?
Buddhist philosophy classifies all materials in the universe into 3 groups, namely non-living materials, living non-sentient organisms and sentient living beings (Dalai Lama: Universe in a single atom). According to Bible, ‘god created man of the dust of the ground and breathed into his nostrils the breath of life, and man became a living soul’ (Genesis 2:7). It implies that soul entered the body at the time of first breath. Most prolife abortion opponents believe that fetus receives the soul at the time of conception.
At the time of conception, the union of a sperm with an egg takes place to form a single fertilized cell or zygote. Multitude of cell divisions later the single cell becomes an embryo or fetus. Only after birth does the fetus able to breathe air independently. It is said that the entry of soul into the new born causes the first cry of the baby. The complete program for this development is inscribed in the genome of the organism.
The genome is a string of nucleic acid made up of 4 different kinds of bases. A combination of three tandem bases code for a letter in the genomic language, with 64 possible letters. The physical nature of an organism is written in this language, called the genetic code.
The genetic code is embedded in the DNA of each cell of the organism (except RNA in some viruses). It was thought that there will be more number of genes with increasing complexity of the higher organism. The estimated number of genes for humans was over 100,000 in 1995 at the initiation human genome project. That estimate steadily decreased with the publication of the draft genome sequence in 2003. Current estimate of number of human genes is between 21,000 and 25,000. It was found that we, humans, differ from Chimpanzee by only 2% of the genomes sequence! Yet how such diversity between the two species is achieved?
Every individual resembles its parents in some respects but differs from them in others. Evolution is the development of dissimilarities between the ancestral and the descendant populations. The mechanisms which determine the similarities and dissimilarities between parents and offspring constitute the subject matter of genetics. Researchers recently deciphered the genetic basis of dog hair coat, a complex trait, from a study of 80 different breeds. They found that just 3 genes could account for all possible combinations of dog hair patterns.
The evolving understanding of genetics and genomic of inheritance and variation is that it is not just the physical number of differences in genes but a combinatorial effect of these gene products and their temporal and spatial expression that is important. Is there a super genetic code at play orchestrating these?
We cannot prove or disprove how life originated on earth, with our current understanding of scientific materialism. Was it formed de novo spontaneously from the crucible of evolution of earth? Was it planted by some asteroids carrying microbes from a distant galaxy? Or is there some cosmic intelligence?
Synthetic biology, the creation of new or alternate forms of life by genetic engineering, has taken off since 1971 when Ananda Chakraborty first created an oil eating bacteria. But so far, no one has not been able to create self replicating organism completely from scratch.
Recently, researchers at the not-for-profit J Craig Venter Institute in Rockville, Maryland, USA have identified a set of minimum genes essential for independent existence and replication of an organism. These fewest possible gene set which allows an organism to grow, replicate and multiply independently was identified by chemical knockout studies of the simplest microbes in existence, Mycoplasma genitalium, which causes urinary tract infections in humans. This knowledge will allow synthetic biologists to create living organisms almost from scratch, and may help to understand molecular mechanisms fundamental to life.
While creation of a simple life form, able to do specific defined functions or self replication may be achievable, creating a sentient being is altogether a different matter. What is soul and consciousness? At what stage of its development does a sentient being get its soul or consciousness?
Buddhist philosophy classifies all materials in the universe into 3 groups, namely non-living materials, living non-sentient organisms and sentient living beings (Dalai Lama: Universe in a single atom). According to Bible, ‘god created man of the dust of the ground and breathed into his nostrils the breath of life, and man became a living soul’ (Genesis 2:7). It implies that soul entered the body at the time of first breath. Most prolife abortion opponents believe that fetus receives the soul at the time of conception.
At the time of conception, the union of a sperm with an egg takes place to form a single fertilized cell or zygote. Multitude of cell divisions later the single cell becomes an embryo or fetus. Only after birth does the fetus able to breathe air independently. It is said that the entry of soul into the new born causes the first cry of the baby. The complete program for this development is inscribed in the genome of the organism.
The genome is a string of nucleic acid made up of 4 different kinds of bases. A combination of three tandem bases code for a letter in the genomic language, with 64 possible letters. The physical nature of an organism is written in this language, called the genetic code.
The genetic code is embedded in the DNA of each cell of the organism (except RNA in some viruses). It was thought that there will be more number of genes with increasing complexity of the higher organism. The estimated number of genes for humans was over 100,000 in 1995 at the initiation human genome project. That estimate steadily decreased with the publication of the draft genome sequence in 2003. Current estimate of number of human genes is between 21,000 and 25,000. It was found that we, humans, differ from Chimpanzee by only 2% of the genomes sequence! Yet how such diversity between the two species is achieved?
Every individual resembles its parents in some respects but differs from them in others. Evolution is the development of dissimilarities between the ancestral and the descendant populations. The mechanisms which determine the similarities and dissimilarities between parents and offspring constitute the subject matter of genetics. Researchers recently deciphered the genetic basis of dog hair coat, a complex trait, from a study of 80 different breeds. They found that just 3 genes could account for all possible combinations of dog hair patterns.
The evolving understanding of genetics and genomic of inheritance and variation is that it is not just the physical number of differences in genes but a combinatorial effect of these gene products and their temporal and spatial expression that is important. Is there a super genetic code at play orchestrating these?
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