Sequence Of Nucleotide Bases In The Dna example essay topic

DNA CHIPS AND THE PHARMACEUTICAL INDUSTRY INTRODUCTION When future historians look back on the greatest scientific advancements of the 20th century, they will without a doubt focus on only three events: the Apollo Moon landing, the invention of the microprocessor, and possibly the greatest scientific endeavor yet, genomics, the science of identifying genes and how they work in humans. It is possibly not a total coincidence then that two of this centuries greatest advancements have grown out of the same cradle of technology, Silicon Valley. The first advancement was the invention of the microprocessor, and the second was the invention of the DNA chip, also called the DNA array or bio chip. These DNA chips are the newest tools being used in the study of genomics. DNA chips are changing the way researchers analyze the genetic make-up of cells, and will soon render traditional pharmaceutical research obsolete. This allows for whole new generations of drugs that will be made to combat diseases by effecting changes in a their specific genetic design.

PROBLEM STATEMENT Currently the pharmaceutical industry is a very high risk industry in which fewer than one in ten promising drug products ever makes it through the testing phase and onto the shelves at the local pharmacy. The effect is that the production of a new drug is almost like a guessing game that may or may not produce any profit. A Company may have a long list of chemicals that could make possible drugs to treat a specific affliction, but by the time they narrow the list down, and do the necessary research and testing, they may have already spent possibly millions of dollars. In the end they may not even be left with a viable drug to market.

BACKGROUND This section is designed to educate the reader on some of the background information needed to understand the nature of DNA chips, as well as to appreciate the benefits the chips could bring to pharmaceutical research. This section consists of the following sections: The Definition of DNA Chips, and The Pharmaceutical Industry Today. The Definition of DNA Chips DNA chips bear an amazing resemblance to microchips. DNA chips are basically pieces of silicon that are layered with a dense checkerboard-like grid of sites called features [2]. There are typically anywhere from 100,000 to 500,000 of these features on any given 2 X 2 cm DNA chip.

Attached at each feature are millions of copies of a single segment of DNA, which acts as a DNA probe. Each segment of DNA can range from a few nucleotides, to millions. Nucleotides are the chemical building blocks of DNA. There are only four nucleotides that make up every single strand of DNA in every living creature: adenine, guanine, cytosine, and thymine.

Any genetic material being tested is first labeled with a fluorescent marker. When the marked DNA is applied to the DNA chip, any strands of marked DNA whose nucleotide sequence is complimentary to the sequence of a given DNA probe, will hybridize to the DNA probe and hence 'stick' to the chip. Any other marked DNA that does not compliment one of the particular sequences of a probe on the chip, will not stick, and can be washed away. Even DNA segments that partially complement and bond with the DNA of the probe, will be washed away with a 97 percent success rate.

Carefully designed arrays of DNA probes can give the DNA chip the ability to represent an entire genes nucleotide sequence. Such chips can reveal visually, via hundred thousand-dollar read-out displays, whether the DNA sample being tested differs by even a single nucleotide from the standard version. When there may be millions of nucleotides in a given sample, being able to identify one that doesn't match is a tremendous feat. The technology that spawned the DNA chip became a reality in the early 1990's, after the commencement of the Human Genome Project (HGP). The HGP was started in 1990 and is one of the most ambitious endeavors ever undertaken by mankind. It is a government funded project whose two major goals are to identify the 80,000 to 100,000 genes in human DNA, and to determine the nucleotide sequences of the 3 billion or so chemical bases that make-up human DNA.

The genes in human DNA largely determine every physical characteristic, and possibly many mental characteristics that define what a human being is. It is our genes that make us different from every other living creature. The chemical codes that make up these genes are in effect a 'book of life. ' The HGP was expected to be completed in the year 2005, but several technological advancements, such as DNA chips, have pushed the expected completion date at least 4 years forward to 2001.

The major difference between DNA chips and previous DNA sequencing technologies is not in what the chips do, but in the manner of how it is done. Previous methods of gene sequencing focused on analyzing only one gene at a time, and to analyze one could take several weeks. By utilizing DNA chip technology, literally thousands of genes can be analyzed and identified simultaneously and all this can be accomplished within days or even hours. Previous technologies would cost thousands of dollars to analyze one gene, but DNA chips can accomplish the same task for a hundred dollars or less per gene. The idea behind DNA chips is that the sequence of a standard DNA sample must be known before a chip can be of use. Once this sequence is identified a chip is tailor-made to search for that particular sequence or sequences, and match it to the DNA of a sample.

It is feasible that within the next decade, after the human genetic design has been analyzed and established, a DNA chip will be made that will have the ability to analyze a few cell samples of an individual, and within hours or possibly even minutes, determine if and exactly how that persons gene make-up differs from the standard human gene make-up. There could possibly be hundreds of genetic differences. Any one of these differences could be the cause of a specific type of ailment or cause a genetic predisposition to a certain type of ailment. So in effect, this technology gives science the potential ability to analyze the specific genetic make-up of every living creature on earth, by determining how that creatures genetic make-up differs from a standard known genetic make-up.

Once all of this information is known, the possibilities for DNA chips, and hence the market for DNA chips, becomes endless. One of the greatest and most obvious markets for the DNA chip will be its use in the pharmaceutical industry. In order to understand the potential benefits of the chips use in the pharmaceutical industry, one must first understand the nature of the industry as it stands today. The pharmaceutical industry Today The pharmaceutical industry today is a huge multi-billion dollar industry that is constantly growing and changing. Pharmaceutical companies, such as Merck, Glaxo Wellcome, and Bristol-Myers Squibb, are constantly trying to come up with new drugs to get out onto the market.

However, there are many problems with the way these new drugs are developed. The main problem being the high level of risk involved when trying to develop new drugs. For the most part, the only companies that can afford to produce drugs are the multi-billion dollar companies, such as Merck. These companies usually employ the strategy of spreading the high risks of drug development over many different projects. As a consequence, many investors are apprehensive about smaller pharmaceutical companies, even if they appear to be on the verge of developing a promising product. Because of this trial and error factor, it has been estimated that the cost of bringing a lead drug candidate to the market is in the range of 260 to 320 million dollars.

Because of the high risk involved, and the high costs of developing and testing new drugs, only about three out of ten drugs that finally make it to the pharmacy shelves ever recover the average development costs of new medicines. Also, the patents on about 30 major drugs will be expiring within the next three years, so there is incredible pressure on companies to develop new major drugs to keep their profits up. In order for a company to develop a drug for a specific illness, there must be some knowledge of what is causing the illness in the first place. The cause of the illness is usually a chemical, bacterium, or virus that is causing some sort of troubles within a person's body. Once this cause is identified, a list of chemical candidates must be created, that can yield some benefits. Lead candidates should meet the following criteria: o Candidates should be able to be synthesized with the fewest number of steps. o The steps of synthesis should be as least complicated and difficult as possible to utilize a source substance. o The base substance should be easily available at a reasonable cost. o The synthesis process should lend itself to large scale manufacturing [3].

A new drug candidate must be able to have the same beneficial effect on a large segment of the target population. If a drug only works on a small specific group of the target population, then the drug will probably not be FDA approved. Also, a drug that does not demonstrate its effectiveness over a large segment of the target population will probably not be very cost effective, considering the average costs of developing new drugs. A drug candidate must demonstrate a large separation between an effective dose and a dose that will produce any adverse side effects. The amount of adverse side effects possible, due to the drug's usage, must be kept to a minimal. The above listed criteria are just a small percent of the standards a drug candidate must meet before being approved for human testing.

Once all of the necessary criteria are met, then the drug can go into the final phase of testing, human tests. By the time a manufacturer has reached this phase, they have already spent millions of dollars. The average time spent going from a drug's discovery to a market launch could be anywhere from 4 to 12 years. DNA DNA, or Deoxyribonucleic Acid, is described, in Encarta Encyclopedia as a genetic material of all cellular organisms and most viruses. DNA carries the information needed to direct protein synthesis and replication. Protein synthesis is the production of the proteins needed by the cell or virus for its activities and development.

Replication is the process by which DNA copies itself for each descendant cell or virus, passing on the information needed for protein synthesis. In most cellular organisms, DNA is organized on chromosomes located in the nucleus of the cell. A molecule of DNA consists of two chains, strands composed of a large number of nucleotides, that are linked together to form a chain. These chains look like a twisted ladder and are called a double helix. Each nucleotide consists of three units: sugar molecules called deoxyribose, a phosphate group, and one of four different nitrogen containing compounds, also called bases. The four are adenine (A), guanine (G), thymine (T), and cytosine (C).

The deoxyribose molecule occupies the center of the nucleotide, with the phosphate group on one side and a base on the other. The phosphate group of each nucleotide is also linked to the deoxyribose of the adjacent nucleotide in the chain. These linked deoxyribose-phosphate subunits form the side rails of the ladder. The bases face inward toward each other, forming the steps of the ladder. The nucleotides in one DNA strand have a specific association with the corresponding nucleotides in the other DNA strand. Because of the chemical affinity of the bases, nucleotides containing adenine are always paired with nucleotides containing thymine, and nucleotides containing cytosine are always paired with nucleotides containing guanine.

The complementary bases are joined to each other by weak chemical bonds called hydrogen bonds. DNA carries the instructions for the production of proteins. A protein is composed of smaller molecules called amino acids, and the structure and function of the protein is determined by the sequence of its amino acids. The sequence of amino acids, in turn, is determined by the sequence of nucleotide bases in the DNA.

A sequence of three nucleotide bases, called a triplet, is the genetic code word, or codon, that specifies a particular amino acid. For instance, the triplet GAC (guanine, adenine, and cytosine) is the codon for the amino acid leucine, and the triplet CAG (cytosine, adenine, and guanine) is the codon for the amino acid valine. A protein consisting of 100 amino acids is thus encoded by a DNA segment consisting of 300 nucleotides. Of the two poly nucleotide chains that form a DNA molecule, only one strand, called the sense strand, contains the information needed for the production of a given amino acid sequence.

The other strand aids in replication. Protein synthesis begins with the separation of a DNA molecule into two strands. In a process called transcription, a section of the sense strand acts as a template, or pattern, to produce a new strand called messenger RNA (m RNA). The m RNA leaves the cell nucleus and attaches to the ribosomes, specialized cellular structures that are the sites of protein synthesis. Amino acids are carried to the ribosomes by another type of RNA, called transfer RNA (t RNA). In a process called translation, the amino acids are linked together in a particular sequence, dictated by the m RNA, to form a protein.

A gene is a sequence of DNA nucleotides that specify the order of amino acids in a protein via an intermediary m RNA molecule. Substituting one DNA nucleotide with another containing a different base causes all descendant cells or viruses to have the altered nucleotide base sequence. As a result of the substitution, the sequence of amino acids in the resulting protein may also be changed. Such a change in a DNA molecule is called a mutation. Most mutations are the result of errors in the replication process. Exposure of a cell or virus to radiation or to certain chemicals increases the likelihood of mutations.

Replication In most cellular organisms, replication of a DNA molecule takes places in the cell nucleus and occurs just before the cell divides. Replication begins with the separation of the two poly nucleotide chains, each of which then acts as a template for the assembly of a new complementary chain. As the old chains separate, each nucleotide in the two chains attracts a complementary nucleotide that has been formed earlier by the cell. The nucleotides are joined to one another by hydrogen bonds to form the rungs of a new DNA molecule.

As the complementary nucleotides are fitted into place, an enzyme called DNA polymerase links them together by bonding the phosphate group of one nucleotide to the sugar molecule of the adjacent nucleotide, forming the side rail of the new DNA molecule. This process continues until a new poly nucleotide chain has been formed alongside the old one, forming a new double-helix molecule. Research and Applications The study of DNA is still under way, and the results of such research are being applied in many disciplines. The Human Genome Project in the United States is a federally funded effort to determine the sequence of bases of the three billion pairs of nucleotides composing the human genetic material. The project will make possible the analysis of the mutations that cause genetic diseases and so will provide information needed to develop medicines and procedures for treating these diseases. Forensic science uses techniques developed in DNA research to identify individuals who have committed crimes.

DNA from semen, skin, or blood taken from the crime scene can be compared with the DNA of a suspect, and the results can be used in court as evidence. Techniques of DNA manipulation are used in farming, in the form of genetic engineering and biotechnology. Strains of crop plants to which genes have been transferred may produce higher yields and may be more resistant to insects. Cattle have been similarly treated to increase milk and beef production, as have hogs, to yield more meat and less fat.