**2. Genomic medicine**

This chapter describes the novel drug design based on the genetic makeup of a patient. My main focus is on two major areas, and they are diagnostic and novel drug design to treat these diseases. Today, we are treated with the same medicine for the same disease as if we all have the identical genomes. In fact, no two people look alike and no two genomes are alike. Our genome is made of six billion four hundred million nucleotides, and in almost every 1000 nucleotides, we find a variant and in the entire script, we find 3.4 million variants called the SNP (single-nucleotide polymorphism). Each of us has a unique genetic makeup and requires the development of a specific medicine to treat that disease. This concept is now known as the pharmacogenomic, and it provides a paradigm shift in drug design.

To design a genomic medicine, first we need to sequence the whole genome identifying specific region (genes) which codes for specific proteins. Second, we need to sequence as many genomes as possible (such efforts are undergoing as a Thousand Genome Project, a Million or a Three Million Genome Project) to compare their sequences to identify differences called variants. Then, we need to develop next generation of sequencers to sequence everyone's genome as cheaper and as faster as possible. Next, we need to identify the differences in the genetic scripts, and then, we need to separate bad or abnormal mutated variants responsible for causing diseases. Next, we need to identify rare variants as diagnostic tools responsible for causing rare diseases (young people diseases) such as Parkinson, Huntington, cystic fibrosis, muscular dystrophy, color blindness, sickle cell anemia, etc. called the monogenic or Mendelian diseases. Next, we need to identify the common genetic diseases (old people diseases) such as cancers, cardiovascular diseases, and Alzheimer. First, we generate sequence data and then by comparing we find a correlation between variants and diseases. We can construct a correlation map of all variants responsible for causing all genetic disorders. After diagnosing the diseases, the next most important step is to treat those diseases by novel drug design.

Our work below describes over a quarter of a century's effort by first designing drugs to shut off genes responsible for causing cancers in animals and then we further describe how we translated the animal work in humans. The following pages describe the development of genomic medicine based on the drug design and on the genetic makeup of a patient. I will cover three areas. First, I will provide historical background which describes the early development of medicines to treat diseases. Second, I will describe the rational drug design to treat abnormal mutated genes and the specific nucleotide identified by the human genome sequencing to develop new drugs to treat old diseases, and finally, I will discuss the ethical problems in an attempt to answer the consequences of prolonging human life on planetary resources and environment.

### **3. Historical background**

Since the dawn of human civilization, achieving human longevity has been the dream of every King, every Queen, every Pharos, and every Caesar. But they all died in their 50s by infectious diseases. Then came the science and technology revolution. In 1928, Alexander Flaming, while working on influenza virus, observed that a mold had developed accidently on a staphylococcus culture plate. By killing the bacteria, the mold had created a bacteria-free circle around itself. He was so inspired by the presence of the bacterial free zone that he conducted further experiment and found that the mold culture produced a substance which prevented growth of staphylococci, even when diluted 800 times. He named the

**97**

*The Rational Drug Design to Treat Cancers DOI: http://dx.doi.org/10.5772/intechopen.93325*

per trillion) to provide safe food for consumption.

human lifespan beyond 60 to 70 years.

Human Longevity Project.

active substance penicillin. The discovery of penicillin [1] was followed by a host of new antibiotics such as streptomycin, neomycin, kanamycin, paromomycin, apramycin, tobramycin, amikacin, netilmicin, and gentamicin and dozens of their derivatives which wipeout Gram-positive and Gram-negative bacteria. Misuse and overuse of antibiotics in agriculture resulted in the bacterial resistance. For example, farmers overuse the antibiotics in food-producing animals not only to kill the bacteria in cows, goat, and chicken farms but also use to promote growth in these animals exposing excessive amount of antibiotics residues to humans in their food. We developed a spectroscopic method [2] to detect their residue in PPT (parts

We conquered infectious diseases. We increased our life span from 50 to 60 years. Then came the genetic revolution. We broke the genetic code and unlocked the secrets of life. Now, we are ready to manipulate life not only to clean up our environmental pollution but also to produce new food, new fuel, and new medicine to treat every disease known to mankind. We also succeeded in increasing

Next, we read the entire book of human life. We read the total genetic information that makes the human life; we completed the Human Genome Project. Next, we sequenced the human genome, that is, we read the number of nucleotides and the order in which they are arranged. With advancement in science and technology, we sequenced the human genome cheaper and faster using the next-generation sequencers such as nanopore. Then, we completed the 1000 Human Genome Project. We are able to compare the reference sequence of every gene with the 1000 copies of the same gene from different individuals to identify differences. These differences are called variants. If the good variant came from the pancreas, it produces insulin which is used to treat diabetes. If the variant came from an abnormal mutated gene, it is responsible for causing common diseases such as cancers, cardiovascular diseases, or Alzheimer. Soon, we will prepare a variant map of the entire genome to identify all 6000 diseases; then, we can design drugs to treat these diseases by shutting off their genes. The Thousand Genome Project will help us single out the rare mutation responsible for causing rare genetic diseases such as Parkinson with precision and accuracy. With advent of new technologies, we embark on the more ambitious project such as The Human Brain Project and The

Next, I will attempt to answer an important question about how to design drugs to treat diseases to save human life by using the information available from the Human Genome Project. How many diseases we inherit from our parents? We identified good and bad genes in our genome. We wonder if bad mutations are written on our DNA. Is the secret hidden in the long string of four nucleotides text on a three-letter codon carrying 24,000 genes in 46 chromosomes in our genome containing six billion four hundred million nucleotides? Could we identify the genetic variants responsible for our diseases by comparing the whole-genome sequence of the centenarians with the 1000 Human Genome Project completed by US and a Million Human Genome Project to be completed by European and a three Million Human Genome Project announced by the Chinese to identify rare alleles responsible for causing rare diseases with accuracy and precision. We want to identify in the whole genome the specific genetic variations and the few nucleotides responsible for our health. As I said above, before the discovery of antibiotics, most people died in their 50s. Today, all infectious diseases are treated with antibiotics. Now, we must treat the old age common diseases such as cancers, cardiac diseases, and Alzheimer. To save human life from these dreadful diseases, we have to design drugs to shut off genes responsible for causing these old age diseases. Next, I will describe how I design drugs to shut off genes which cause brain cancer, glioblastomas. Similar

#### *The Rational Drug Design to Treat Cancers DOI: http://dx.doi.org/10.5772/intechopen.93325*

*Drug Design - Novel Advances in the Omics Field and Applications*

This chapter describes the novel drug design based on the genetic makeup of a patient. My main focus is on two major areas, and they are diagnostic and novel drug design to treat these diseases. Today, we are treated with the same medicine for the same disease as if we all have the identical genomes. In fact, no two people look alike and no two genomes are alike. Our genome is made of six billion four hundred million nucleotides, and in almost every 1000 nucleotides, we find a variant and in the entire script, we find 3.4 million variants called the SNP (single-nucleotide polymorphism). Each of us has a unique genetic makeup and requires the development of a specific medicine to treat that disease. This concept is now known as the

To design a genomic medicine, first we need to sequence the whole genome identifying specific region (genes) which codes for specific proteins. Second, we need to sequence as many genomes as possible (such efforts are undergoing as a Thousand Genome Project, a Million or a Three Million Genome Project) to compare their sequences to identify differences called variants. Then, we need to develop next generation of sequencers to sequence everyone's genome as cheaper and as faster as possible. Next, we need to identify the differences in the genetic scripts, and then, we need to separate bad or abnormal mutated variants responsible for causing diseases. Next, we need to identify rare variants as diagnostic tools responsible for causing rare diseases (young people diseases) such as Parkinson, Huntington, cystic fibrosis, muscular dystrophy, color blindness, sickle cell anemia, etc. called the monogenic or Mendelian diseases. Next, we need to identify the common genetic diseases (old people diseases) such as cancers, cardiovascular diseases, and Alzheimer. First, we generate sequence data and then by comparing we find a correlation between variants and diseases. We can construct a correlation map of all variants responsible for causing all genetic disorders. After diagnosing the diseases,

pharmacogenomic, and it provides a paradigm shift in drug design.

the next most important step is to treat those diseases by novel drug design.

Our work below describes over a quarter of a century's effort by first designing drugs to shut off genes responsible for causing cancers in animals and then we further describe how we translated the animal work in humans. The following pages describe the development of genomic medicine based on the drug design and on the genetic makeup of a patient. I will cover three areas. First, I will provide historical background which describes the early development of medicines to treat diseases. Second, I will describe the rational drug design to treat abnormal mutated genes and the specific nucleotide identified by the human genome sequencing to develop new drugs to treat old diseases, and finally, I will discuss the ethical problems in an attempt to answer the consequences of prolonging human life on planetary

Since the dawn of human civilization, achieving human longevity has been the dream of every King, every Queen, every Pharos, and every Caesar. But they all died in their 50s by infectious diseases. Then came the science and technology revolution. In 1928, Alexander Flaming, while working on influenza virus, observed that a mold had developed accidently on a staphylococcus culture plate. By killing the bacteria, the mold had created a bacteria-free circle around itself. He was so inspired by the presence of the bacterial free zone that he conducted further experiment and found that the mold culture produced a substance which prevented growth of staphylococci, even when diluted 800 times. He named the

**2. Genomic medicine**

**96**

resources and environment.

**3. Historical background**

active substance penicillin. The discovery of penicillin [1] was followed by a host of new antibiotics such as streptomycin, neomycin, kanamycin, paromomycin, apramycin, tobramycin, amikacin, netilmicin, and gentamicin and dozens of their derivatives which wipeout Gram-positive and Gram-negative bacteria. Misuse and overuse of antibiotics in agriculture resulted in the bacterial resistance. For example, farmers overuse the antibiotics in food-producing animals not only to kill the bacteria in cows, goat, and chicken farms but also use to promote growth in these animals exposing excessive amount of antibiotics residues to humans in their food. We developed a spectroscopic method [2] to detect their residue in PPT (parts per trillion) to provide safe food for consumption.

We conquered infectious diseases. We increased our life span from 50 to 60 years. Then came the genetic revolution. We broke the genetic code and unlocked the secrets of life. Now, we are ready to manipulate life not only to clean up our environmental pollution but also to produce new food, new fuel, and new medicine to treat every disease known to mankind. We also succeeded in increasing human lifespan beyond 60 to 70 years.

Next, we read the entire book of human life. We read the total genetic information that makes the human life; we completed the Human Genome Project. Next, we sequenced the human genome, that is, we read the number of nucleotides and the order in which they are arranged. With advancement in science and technology, we sequenced the human genome cheaper and faster using the next-generation sequencers such as nanopore. Then, we completed the 1000 Human Genome Project. We are able to compare the reference sequence of every gene with the 1000 copies of the same gene from different individuals to identify differences. These differences are called variants. If the good variant came from the pancreas, it produces insulin which is used to treat diabetes. If the variant came from an abnormal mutated gene, it is responsible for causing common diseases such as cancers, cardiovascular diseases, or Alzheimer. Soon, we will prepare a variant map of the entire genome to identify all 6000 diseases; then, we can design drugs to treat these diseases by shutting off their genes. The Thousand Genome Project will help us single out the rare mutation responsible for causing rare genetic diseases such as Parkinson with precision and accuracy. With advent of new technologies, we embark on the more ambitious project such as The Human Brain Project and The Human Longevity Project.

Next, I will attempt to answer an important question about how to design drugs to treat diseases to save human life by using the information available from the Human Genome Project. How many diseases we inherit from our parents? We identified good and bad genes in our genome. We wonder if bad mutations are written on our DNA. Is the secret hidden in the long string of four nucleotides text on a three-letter codon carrying 24,000 genes in 46 chromosomes in our genome containing six billion four hundred million nucleotides? Could we identify the genetic variants responsible for our diseases by comparing the whole-genome sequence of the centenarians with the 1000 Human Genome Project completed by US and a Million Human Genome Project to be completed by European and a three Million Human Genome Project announced by the Chinese to identify rare alleles responsible for causing rare diseases with accuracy and precision. We want to identify in the whole genome the specific genetic variations and the few nucleotides responsible for our health. As I said above, before the discovery of antibiotics, most people died in their 50s. Today, all infectious diseases are treated with antibiotics. Now, we must treat the old age common diseases such as cancers, cardiac diseases, and Alzheimer. To save human life from these dreadful diseases, we have to design drugs to shut off genes responsible for causing these old age diseases. Next, I will describe how I design drugs to shut off genes which cause brain cancer, glioblastomas. Similar

rationale could be used to design drugs to shut off genes responsible for causing cardiovascular diseases and Alzheimer.

## **4. Genotype-phenotype correlations**

Our genes are units of inheritance and carry instructions to make proteins, and when the proteins fold, they become reactive and carry out a specific function. Hundreds of proteins interact to make a cell, and millions of cells interact to make a tissue. Hundreds of tissues interact to make an organ, and several organs interact to make a human being. We carry in our body 220 different tissues. The instructions to make tissues are written in our genes. A defected tissue could be identified by looking at the mutation in the genes. We can prevent diseases at a very early stage of our lives. By sequencing a fertilized egg, the genotype, we could identify the mutations responsible for future diseases in tissues, the phenotype. If a patient has a family history of a specific disease, to prevent future generation from inheriting the disease, it is best advice for such families to have conception by in vitro fertilization after making sure that the fertilized egg is free from all abnormal mutations responsible for causing the disease.

Our entire genome, the book of our life, is written in four nucleotides, and they are A (adenine), T (thiamine), G (guanine), and C (cytosine). The chain of these nucleotides forms a double-stranded string of nucleotides, one strand is inherited from our mother and another from our father, running in opposite directions called the DNA (deoxyribonucleotide). According to Francis Crick's Central Dogma [3], double-stranded DNA is transcribed into a single-stranded RNA which is translated in the ribosome into proteins. The discovery of the double helical structure of DNA explained how the information to create life is stored, replicate, evolved, and passed on to the next generation. This discovery opened a new world order of ideas and buried the old explanation of the magical mystical appearance of life on Earth.

The double-stranded DNA explained that the essence of life is information and the information is located on these four nucleotides. Every set of three nucleotides on the mRNA forms a codon which codes for a specific amino acid. The four-letter text of nucleotides forms a three-letter codon which codes for an amino acid. There are 64 different combinations of codons which codes for all 20 amino acids. Sequencing human genome identifies the number of nucleotides and the order in which they are arranged. Less than 2% of our genome contains regulatory region, a piece of DNA, which controls the function of genes. More than 300 regulatory regions have been identified. More than 98% of our genome contains non-coding region used to be called the junk DNA which makes up to 60% of our entire genome. The non-coding regions contains repetitive piece of DNA, which is tightly packed and mostly remain silent. The sequencing of this region showed that the non-coding region is the part of viruses and bacteria picked up by our genome during the millions of years of our evolutionary process. During bacterial or viral infection, the non-coding DNA could unfold transcribing into RNA resulting into hazardous protein which could create havoc for our health.

Genes are the unit of inheritance. As I said above, out of four-letter text, that is A-T and G-C, and three letters code for an amino acid called the codon. The starting codon in a gene is the codon AUG (instead of T nucleotide, we use U nucleotide because thiamin is converted to more water-soluble uracil), which codes for amino acid methionine. Long chain of DNA synthesis begins. The starting codon is followed by a series of hundreds of codons which codes for different amino acids in different species. There are three stop codons, and they are AUG, UGG, and UGA.

**99**

chromosome [4–8].

*The Rational Drug Design to Treat Cancers DOI: http://dx.doi.org/10.5772/intechopen.93325*

restore health.

that gene. Sequencing is like extracting gold from its ore.

Once the stop codons appear, DNA synthesis stops. Bacteria and viruses have short codon chain. The longest chain is in a gene of Duchenne muscular dystrophy, a neurological disease whose chain extends to two and a half million codons. Once a gene is identified, using restriction enzymes, like EcoR1, we can cut, paste, and copy all genes individually making a restriction site map. Once a single gene is isolated, we could compare the sequence of this gene with the Thousand Genome Project to identify abnormal mutation responsible for the disease and design drugs to shut off

Let us examine the sequence of the genome of human egg and sperm. An egg contains a single strand of 164 million nucleotide bases carrying 1144 genes, while the human sperm contains a single strand of 59 million nucleotide bases carrying 214 genes. When comparing the sequence of an egg or sperm with sequence of the 1000 eggs and sperms of different people, we notice changes. These changes are called variants. These variants are mutations caused by radiations, chemical and environmental pollution, viral infection, or genetic inheritance resulting in rare diseases. Once a bad gene is identified, sequencing will identify the abnormal nucleotide. Now, we can design drug to bind to this nucleotide and shut off its function. We present in the "Cancers" section below a novel drug design. Using aziridines and carbamate how we design drugs to shut off these genes to

Although we are allowed to shut off and remove bad genes, we are not allowed to introduce good genes in the egg and sperm to enhance the abilities of egg and sperm because modification introduced in the egg and sperm will pass on to the next 1000 generations. For this reason, germ line gene therapy is forbidden in all countries. At this time, we cannot answer a simple question. Are we to determine the quality of

We cannot design novel drugs unless we find the abnormal mutations responsible for causing that disease. The reading of the total genetic information that makes us human is called the human genome. The reading of the entire book of our life is authorized by the US Congress under The Human Genome Project. It will answer the most fundamental question we have asked ourselves since the dawn of human civilization. What does it mean to be human? What is the nature of memory and our consciousness? Our development from a single cell to a complete human being? The biochemical nature of our senses and the process of our aging? The scientific basis of our similarity and dissimilarity: similarity is that all living creatures from a tiny blade of grass to the mighty elephant including man, mouse, monkey, mosquitos, and microbes are all made of the same chemical building blocks, yet we are so diverse that no two individuals are alike even identical twins are not exactly identi-

In 1990, US Congress authorized 3 billion dollars to NIH to decipher the entire human genome under the title, "The Human Genome Project." We found that our genome contains six billion four hundred million nucleotide bases, half comes from our father and another half comes from our mother. Less than 2% of our genome contains genes which code for proteins. The other 98% of our genome contains switches, promoters, terminators, etc. The 46 chromosomes present in each cell of our body are the greatest library of the Human Book of Life on planet Earth. The chromosomes carry genes which are written in nucleotides. Before sequencing (determining the number and the order of the four nucleotides on a chromosome), it is essential to know how many genes are present on each chromosome in our genome. The Human Genome Project has identified not only the number of nucleotides on each chromosome but also the number of genes on each

life of individuals who will not even be born before the century is over?

cal, they grow up to become two separate individuals.

#### *The Rational Drug Design to Treat Cancers DOI: http://dx.doi.org/10.5772/intechopen.93325*

*Drug Design - Novel Advances in the Omics Field and Applications*

cardiovascular diseases and Alzheimer.

**4. Genotype-phenotype correlations**

responsible for causing the disease.

rationale could be used to design drugs to shut off genes responsible for causing

Our genes are units of inheritance and carry instructions to make proteins, and when the proteins fold, they become reactive and carry out a specific function. Hundreds of proteins interact to make a cell, and millions of cells interact to make a tissue. Hundreds of tissues interact to make an organ, and several organs interact to make a human being. We carry in our body 220 different tissues. The instructions to make tissues are written in our genes. A defected tissue could be identified by looking at the mutation in the genes. We can prevent diseases at a very early stage of our lives. By sequencing a fertilized egg, the genotype, we could identify the mutations responsible for future diseases in tissues, the phenotype. If a patient has a family history of a specific disease, to prevent future generation from inheriting the disease, it is best advice for such families to have conception by in vitro fertilization after making sure that the fertilized egg is free from all abnormal mutations

Our entire genome, the book of our life, is written in four nucleotides, and they are A (adenine), T (thiamine), G (guanine), and C (cytosine). The chain of these nucleotides forms a double-stranded string of nucleotides, one strand is inherited from our mother and another from our father, running in opposite directions called the DNA (deoxyribonucleotide). According to Francis Crick's Central Dogma [3], double-stranded DNA is transcribed into a single-stranded RNA which is translated in the ribosome into proteins. The discovery of the double helical structure of DNA explained how the information to create life is stored, replicate, evolved, and passed on to the next generation. This discovery opened a new world order of ideas and buried the old explanation of the magical mystical appearance of life on Earth.

The double-stranded DNA explained that the essence of life is information and the information is located on these four nucleotides. Every set of three nucleotides on the mRNA forms a codon which codes for a specific amino acid. The four-letter text of nucleotides forms a three-letter codon which codes for an amino acid. There are 64 different combinations of codons which codes for all 20 amino acids. Sequencing human genome identifies the number of nucleotides and the order in which they are arranged. Less than 2% of our genome contains regulatory region, a piece of DNA, which controls the function of genes. More than 300 regulatory regions have been identified. More than 98% of our genome contains non-coding region used to be called the junk DNA which makes up to 60% of our entire

genome. The non-coding regions contains repetitive piece of DNA, which is tightly packed and mostly remain silent. The sequencing of this region showed that the non-coding region is the part of viruses and bacteria picked up by our genome during the millions of years of our evolutionary process. During bacterial or viral infection, the non-coding DNA could unfold transcribing into RNA resulting into

Genes are the unit of inheritance. As I said above, out of four-letter text, that is A-T and G-C, and three letters code for an amino acid called the codon. The starting codon in a gene is the codon AUG (instead of T nucleotide, we use U nucleotide because thiamin is converted to more water-soluble uracil), which codes for amino acid methionine. Long chain of DNA synthesis begins. The starting codon is followed by a series of hundreds of codons which codes for different amino acids in different species. There are three stop codons, and they are AUG, UGG, and UGA.

hazardous protein which could create havoc for our health.

**98**

Once the stop codons appear, DNA synthesis stops. Bacteria and viruses have short codon chain. The longest chain is in a gene of Duchenne muscular dystrophy, a neurological disease whose chain extends to two and a half million codons. Once a gene is identified, using restriction enzymes, like EcoR1, we can cut, paste, and copy all genes individually making a restriction site map. Once a single gene is isolated, we could compare the sequence of this gene with the Thousand Genome Project to identify abnormal mutation responsible for the disease and design drugs to shut off that gene. Sequencing is like extracting gold from its ore.

Let us examine the sequence of the genome of human egg and sperm. An egg contains a single strand of 164 million nucleotide bases carrying 1144 genes, while the human sperm contains a single strand of 59 million nucleotide bases carrying 214 genes. When comparing the sequence of an egg or sperm with sequence of the 1000 eggs and sperms of different people, we notice changes. These changes are called variants. These variants are mutations caused by radiations, chemical and environmental pollution, viral infection, or genetic inheritance resulting in rare diseases. Once a bad gene is identified, sequencing will identify the abnormal nucleotide. Now, we can design drug to bind to this nucleotide and shut off its function. We present in the "Cancers" section below a novel drug design. Using aziridines and carbamate how we design drugs to shut off these genes to restore health.

Although we are allowed to shut off and remove bad genes, we are not allowed to introduce good genes in the egg and sperm to enhance the abilities of egg and sperm because modification introduced in the egg and sperm will pass on to the next 1000 generations. For this reason, germ line gene therapy is forbidden in all countries. At this time, we cannot answer a simple question. Are we to determine the quality of life of individuals who will not even be born before the century is over?

We cannot design novel drugs unless we find the abnormal mutations responsible for causing that disease. The reading of the total genetic information that makes us human is called the human genome. The reading of the entire book of our life is authorized by the US Congress under The Human Genome Project. It will answer the most fundamental question we have asked ourselves since the dawn of human civilization. What does it mean to be human? What is the nature of memory and our consciousness? Our development from a single cell to a complete human being? The biochemical nature of our senses and the process of our aging? The scientific basis of our similarity and dissimilarity: similarity is that all living creatures from a tiny blade of grass to the mighty elephant including man, mouse, monkey, mosquitos, and microbes are all made of the same chemical building blocks, yet we are so diverse that no two individuals are alike even identical twins are not exactly identical, they grow up to become two separate individuals.

In 1990, US Congress authorized 3 billion dollars to NIH to decipher the entire human genome under the title, "The Human Genome Project." We found that our genome contains six billion four hundred million nucleotide bases, half comes from our father and another half comes from our mother. Less than 2% of our genome contains genes which code for proteins. The other 98% of our genome contains switches, promoters, terminators, etc. The 46 chromosomes present in each cell of our body are the greatest library of the Human Book of Life on planet Earth. The chromosomes carry genes which are written in nucleotides. Before sequencing (determining the number and the order of the four nucleotides on a chromosome), it is essential to know how many genes are present on each chromosome in our genome. The Human Genome Project has identified not only the number of nucleotides on each chromosome but also the number of genes on each chromosome [4–8].

The following list provides the details composition of each chromosome including the number of nucleotides and the number of genes on each chromosome.

We found that chromosome-1 is the largest chromosome carrying 263 million A, T, G, and C nucleotide bases and has only 2610 genes. Chromosome-2 contains 255 million nucleotide bases and has only 1748 genes. Chromosome-3 contains 214 million nucleotide bases and carries 1381 genes. Chromosome-4 contains 203 million nucleotide bases and carries 1024 genes. Chromosome-5 contains 194 million nucleotide bases and carries 1190 genes. Chromosome-6 contains 183 million nucleotide bases and carries 1394 genes. Chromosome-7 contains 171 million nucleotide bases and carries 1378 genes. Chromosome-8 contains 155 million nucleotide bases and carries 927 genes. Chromosome-9 contains 145 million nucleotide bases and carries 1076 genes. Chromosome-10 contains 144 million nucleotide bases and carries 983 genes. Chromosome-11 contains 144 million nucleotide bases and carries 1692 genes. Chromosome-12 contains 143 million nucleotide bases and carries 1268 genes. Chromosome-13 contains 114 million nucleotide bases and carries 496 genes. Chromosome-14 contains 109 million nucleotide bases and carries 1173 genes. Chromosome-15 contains 106 million nucleotide bases and carries 906 genes. Chromosome-16 contains 98 million nucleotide bases and carries 1032 genes. Chromosome-17 contains 92 million nucleotide bases and carries 1394 genes. Chromosome-18 contains 85 million nucleotide bases and carries 400 genes. Chromosome-19 contains 67 million nucleotide bases and carries 1592 genes. Chromosome-20 contains 72 million nucleotide bases and carries 710 genes. Chromosome-21 contains 50 million nucleotide bases and carries 337 genes. Chromosome-22 contains 56 million nucleotides and carries 701 genes. Finally, the sex chromosome of all female called the (X) contains 164 million nucleotide bases and carries 1141 genes. The male sperm chromosome contains 59 million nucleotide bases and carries 255 genes.

If you add up all genes in the 23 pairs of chromosomes, they come up to 26,808 genes and yet we keep on mentioning 24,000 genes needed to keep us function normally. As I said above, a gene codes for a protein, not all 24,000 genes code for proteins. It is estimated that less than 19,000 genes code for protein. Because of the alternative splicing, each gene codes for more than one protein. All functional genes in our body make less than 50,000 proteins which interact in millions of different ways to give a single cell. Millions of cells interact to give a tissue, hundreds of tissues interact to give an organ, and several organs interact to make a human.

Not all genes act simultaneously to make us function normally. Current studies show that a minimum of 2000 genes are enough to keep human function normally; the remaining genes are backup support system and they are used when needed. The non-functional genes are called the pseudo genes. For example, millions of years ago, humans and dogs shared some of the same ancestral genes; we both carry the same olfactory genes, only in dogs, they still function to search for food. Since humans do not use these genes to smell for searching food, these genes are broken and lost their functions, but we still carry them. We call them pseudo genes. Recently, some Japanese scientists have activated the pseudo genes; this work may create ethical problem in future as more and more pseudo genes are activated. Nature has good reasons to shut off those pseudo genes.

Next, we converted the analog language biology to the digital language of computer, that is, from A-T and G-C nucleotides to numbers 0 and 1. Now, we can write a program and design a computer to read the book of life faster and faster. Today, we can read our entire genome in 1 day at a cost of 1000 dollars. We can also upload

**101**

*The Rational Drug Design to Treat Cancers DOI: http://dx.doi.org/10.5772/intechopen.93325*

**5. Reactive and predictive medicine**

as the reactive medicine.

the true genomic medicine.

our digitized genome on the computer. Once uploaded on the Website, our genome could travel with the speed of light to anywhere in the world or in the universe.

Once the good and bad genes are identified, we learned that the good genes code for good proteins which keep us healthy and the bad genes produce bad proteins that make us sick. Using good genes, we make good protein to treat diseases such as insulin is used to treat diabetes. On the other hand, we could identify bad gene and design drugs to shut off bad genes to prevent diseases. This starts a new era of genomic medicine based on differences of the genetic make of each individual.

The double-stranded DNA in the normal cell, the autosome, is retained with the individual. When the person dies, the genome dies with him. On the other hand, the DNA in a germ line cell lives on for generations. Through egg and sperm cells, the DNA is passed on to the future generations, that is, the information is passed on from parents to the fetus in different combinations for generation after generation. A sperm, the Y-chromosome, is made of a single string of 59 million nucleotide bases and carry 231 genes, while an egg, the X-chromosome, is made of a single string of 164 million nucleotide bases and carry 1144 genes. Neither two sperms nor any two eggs are alike. Once the egg is fertilized, the nucleotides and genes are exchanged (recombination occurs) among nucleotides forming a double-stranded DNA. Now, each string is a complete genome. During replication, each string separates and picks up the complimentary nucleotide bases (such as nucleotide A picks up T and G picks up C) from the nucleotide pool and forms two double-stranded DNA forming two daughter cells. The two strands of each chain run in opposite directions.

Reactive medicine is the treatment of a disease after its symptoms are revealed

A specific example is as follows: suppose your physician finds that you are sick with high temperature and high blood pressure, he prescribes Plavix a medicine of standard treatment for lowing your blood pressure and temperature. It is a reactive medicine. You receive treatment after your illness is diagnosed. Plavix is a useful drug for treating high blood pressure, but it does not respond in 15% of the patients. In treating reactive medicine, we do not really know what is going on in the body of those patients until after sequencing their genome, and identifying the abnormal mutation in their genetic makeup and then designing drugs to treat those patients is

Predictive medicine, on the other hand, is the treatment of a disease long before

its onset by examining your normal genomic script of the effected organ from your book of life and comparing its entire script with the genome of a sick patient. Spelling errors in our genome are the mutations responsible for causing diseases. The difference between the reactive medicine and the predictive medicine is whether you have the disease or you will come down with the disease because you are carrying a mutation which could become activated and make you sick. Genomic

and the full-blown disease appears. During your annual health checkup, your physicians order a number of tests. For example, if you are a 40-year-old male and go to the doctor, he prescribed a PSA (prostate-specific antigen) test for the early signs of prostate cancer, if you are a 40-year-old woman, your doctor prescribes the mammograms for the early signs of breast cancer, and if you are 50 years old, he prescribes the colonoscopy for colon cancer. Once the symptoms are revealed, the standard treatment is prescribed for a disease such as surgery, radiations treatment, or chemotherapy. The treatment after the appearance of its symptoms is considered

#### *The Rational Drug Design to Treat Cancers DOI: http://dx.doi.org/10.5772/intechopen.93325*

*Drug Design - Novel Advances in the Omics Field and Applications*

The following list provides the details composition of each chromosome includ-

We found that chromosome-1 is the largest chromosome carrying 263 million A, T, G, and C nucleotide bases and has only 2610 genes. Chromosome-2 contains 255 million nucleotide bases and has only 1748 genes. Chromosome-3 contains 214 million nucleotide bases and carries 1381 genes. Chromosome-4 contains 203 million nucleotide bases and carries 1024 genes. Chromosome-5 contains 194 million nucleotide bases and carries 1190 genes. Chromosome-6 contains 183 million nucleotide bases and carries 1394 genes. Chromosome-7 contains 171 million nucleotide bases and carries 1378 genes. Chromosome-8 contains 155 million nucleotide bases and carries 927 genes. Chromosome-9 contains 145 million nucleotide bases and carries 1076 genes. Chromosome-10 contains 144 million nucleotide bases and carries 983 genes. Chromosome-11 contains 144 million nucleotide bases and carries 1692 genes. Chromosome-12 contains 143 million nucleotide bases and carries 1268 genes. Chromosome-13 contains 114 million nucleotide bases and carries 496 genes. Chromosome-14 contains 109 million nucleotide bases and carries 1173 genes. Chromosome-15 contains 106 million nucleotide bases and carries 906 genes. Chromosome-16 contains 98 million nucleotide bases and carries 1032 genes. Chromosome-17 contains 92 million nucleotide bases and carries 1394 genes. Chromosome-18 contains 85 million nucleotide bases and carries 400 genes. Chromosome-19 contains 67 million nucleotide bases and carries 1592 genes. Chromosome-20 contains 72 million nucleotide bases and carries 710 genes. Chromosome-21 contains 50 million nucleotide bases and carries 337 genes. Chromosome-22 contains 56 million nucleotides and carries 701 genes. Finally, the sex chromosome of all female called the (X) contains 164 million nucleotide bases and carries 1141 genes. The male sperm chromosome contains 59 million nucleotide bases and carries

If you add up all genes in the 23 pairs of chromosomes, they come up to 26,808 genes and yet we keep on mentioning 24,000 genes needed to keep us function normally. As I said above, a gene codes for a protein, not all 24,000 genes code for proteins. It is estimated that less than 19,000 genes code for protein. Because of the alternative splicing, each gene codes for more than one protein. All functional genes in our body make less than 50,000 proteins which interact in millions of different ways to give a single cell. Millions of cells interact to give a tissue, hundreds of tissues interact to give an organ, and several organs interact to make

Not all genes act simultaneously to make us function normally. Current studies show that a minimum of 2000 genes are enough to keep human function normally; the remaining genes are backup support system and they are used when needed. The non-functional genes are called the pseudo genes. For example, millions of years ago, humans and dogs shared some of the same ancestral genes; we both carry the same olfactory genes, only in dogs, they still function to search for food. Since humans do not use these genes to smell for searching food, these genes are broken and lost their functions, but we still carry them. We call them pseudo genes. Recently, some Japanese scientists have activated the pseudo genes; this work may create ethical problem in future as more and more pseudo genes are activated.

Next, we converted the analog language biology to the digital language of computer, that is, from A-T and G-C nucleotides to numbers 0 and 1. Now, we can write a program and design a computer to read the book of life faster and faster. Today, we can read our entire genome in 1 day at a cost of 1000 dollars. We can also upload

Nature has good reasons to shut off those pseudo genes.

ing the number of nucleotides and the number of genes on each chromosome.

**100**

255 genes.

a human.

our digitized genome on the computer. Once uploaded on the Website, our genome could travel with the speed of light to anywhere in the world or in the universe.

Once the good and bad genes are identified, we learned that the good genes code for good proteins which keep us healthy and the bad genes produce bad proteins that make us sick. Using good genes, we make good protein to treat diseases such as insulin is used to treat diabetes. On the other hand, we could identify bad gene and design drugs to shut off bad genes to prevent diseases. This starts a new era of genomic medicine based on differences of the genetic make of each individual.

The double-stranded DNA in the normal cell, the autosome, is retained with the individual. When the person dies, the genome dies with him. On the other hand, the DNA in a germ line cell lives on for generations. Through egg and sperm cells, the DNA is passed on to the future generations, that is, the information is passed on from parents to the fetus in different combinations for generation after generation.

A sperm, the Y-chromosome, is made of a single string of 59 million nucleotide bases and carry 231 genes, while an egg, the X-chromosome, is made of a single string of 164 million nucleotide bases and carry 1144 genes. Neither two sperms nor any two eggs are alike. Once the egg is fertilized, the nucleotides and genes are exchanged (recombination occurs) among nucleotides forming a double-stranded DNA. Now, each string is a complete genome. During replication, each string separates and picks up the complimentary nucleotide bases (such as nucleotide A picks up T and G picks up C) from the nucleotide pool and forms two double-stranded DNA forming two daughter cells. The two strands of each chain run in opposite directions.
