The April 14th 2003 became an historical event in DNA science as the National Human Genome Research Institute (NHGRI) in collaboration with the Department of Energy (DoE) and other associates in the International Human Genome Sequencing Consortium finally announced the successful accomplishment of the long awaited results of the Human Genome Project (National Human Genome Research Institute, 2009). Earlier on June 26th 2000, it was announced by the International Human Genome Sequencing Consortium that a rough draft for the complete human genome sequence was complete (National Human Genome Research Institute, 2009).
However, this earlier version lacked some critical information for carrying out quality research by exploiting the entire genome. Since its completion, researchers have carried out extensive investigations on the potential applications of the Human Genome Project. This paper provides an overview of the Human Genome Project focusing on the potential applications in medical science.
Overview of the Human Genome Project Focusing on the Potential Medical Applications
The completion and announcement of the Human Genome Project and the complete sequence of the human genome became a commemoration of the 50th Anniversary since the DNA structure was deciphered by Dr. James Watson and Francis Crick among other scientists (U.S Department of Energy, 2009). Working on the draft that was released on February 12th 2001, scientists from the International Human Genome Sequencing Consortium organized the genome fragments and made it easy for the scientists to carry out research without the need for performing any additional sequencing. For instance, if researchers wanted a specific gene for a certain disease, it became easier to locate it on the long stretch of the accurately sequenced DNA. These developments have largely contributed significant research tools in the area of medical sciences and will continue to be exploited in the discovery of novel drugs specific for individuals as applied in pharmacogenomics.
The Human Genome Project: An Overview
The Human Genome Project became one of the immense international collaborations and perhaps the most extensive biological projects ever to be attempted in human history. A number of researchers worked closely to master the whole sequence of the DNA bases contained in the human genome. The human deoxyribonucleic acid (DNA) consists up to 3,000,000,000 bases which form the entire genome (National Human Genome Research Institute, 2009). Scientists holding discussions at the University of California in Santa Cruz conceived the idea of sequencing the human genome in June 1985. DNA cloning and sequencing tools that earlier developed in 1970s by scientists such as Fred Sanger acted as critical catalysts for the discussion in Santa Cruz (Wellcome Trust Sanger Institute, 2010). Luckily, the period of this conception concurred with the time when computer technology began to be applied in biological systems and genetic applications and DNA sequencing in general benefited significantly as genetic data could be handled with ease around the world.
The Human Genome Project was officially launched in 1990 with major funding from the Department of Energy (DoE) and the United States National Institute of Health (NIH). After years of great collaboration of the laboratories at the NIH and the DoE including other international collaborators, 95 percent of the entire human genome was sequenced (National Human Genome Research Institute, 2009). John Sulston working in the United Kingdom with his colleagues at the Medical Research Center’s (MRC) molecular biology laboratory in Cambridge worked for a number of years mapping the nematode worm genome. Sulston and his team proved that the possibility of coming up with a complete sequence of the worm genome was feasible and this motivated the efforts to work on the human genome project (Wellcome Trust Sanger Institute, 2010).
As efforts to sequence the human genome in the United States progressed, other attempts in the United Kingdom to come up with a complete genome of the worm genome intensified. The MRC organized a partnership with the Wellcome Trust to fund the project of worm sequencing as one of the pilot studies for the Human Genome Project. This new partnership resulted to a much larger sequencing plan to reinforce the Human Genome Research. From this merge, the British arm of the Human Genome Project was eventually formed in 1992 which endeavored in the sequencing efforts. The 1993 saw significant funding from both the MRS and the Wellcome Trust which then led to the official opening of the Sanger Centre (National Human Genome Research Institute, 2009).
The researchers working on the Human Genome Project developed the technique known as the hierarchical shotgun which could enable the achievement of the Human Genome Project’s to cover up to 95 percent of the human genome by the year 2005. Researchers encountered the first challenge of creating a human genomic map which was a cluster of index marks on the human genomic code employed in positioning the sequences of code letters which would result later. Essentially, the researchers split several copies pf the human genome into fragments with each fragment having about 150,000 base pairs or the letters of the code. Fragments that could be grown in the in Escherichia coli bacteria were inserted into artificial chromosomes of the bacteria and thereby replicating the sample DNA so as to create a more stable DNA clone library or resources. It was not however established where the cloned fragment originated from or on which fragment overlapped (National Human Genome Research Institute, 2009).
By the use of special types of enzymes known as the restriction enzymes, the researchers then cut individual clones into fingerprints of fragments which were defined by every sequence of each clone. The scientists could then search for the shared fragments among millions of the fingerprints which would reveal the exact overlaps in the clones. The clones were then assembled into long contiguous regions and then mapped onto the chromosomes of humans. This then resulted into a physical map of human genome which would later solve the hurdles of sequencing. It however required the scientists to break the cloned fragments into very small and manageable chunks each ranging from 1000 to 2000 base pairs in length (Wellcome Trust Sanger Institute, 2010).
The shotgun method which was earlier developed by Fred Sanger and his team was used to sequence the human DNA fragments. Just like in gene mapping, the scientists used overlaps although this time in the genetic code letters, to reorganize determined short sequence stretches. The emerging computer and software technologies allowed for the assembly of the sequence from several short sequences of segments. Within a few years, laboratories in the world started producing sequences of DNA and by 1994; the Sanger Institute alone had made its very first 100,000 human DNA base sequence (National Human Genome Research Institute, 2009). Earlier, researchers had produced about 1,000,000 base sequence of the nematode worm DNA. Generally, the worm project acted as a trailblazer where its practices, methods, ethos and collaborations became critical in the completion of the Human Genome Project.
Medical Applications of the Human Genome Project
The data obtained from the Human Genome Project was made public and it spread around the world. Researchers were anxious to link the benefits of the information obtained from the Human Genome Project in the advancement of medical science and in 1995, scientists from the Sanger Center as well as other international collaborators identified BRCA2, the gene responsible for breast cancer especially among women. Earlier in 1993, researchers from the United States had identified the MSH2 gene which was responsible for the increased incidents of colon cancer among the carriers. Canadian researchers also identified five main FAD gene variants which acted in synergy to confer about 100 percent risk of individuals developing Alzheimer’s disease (National Human Genome Research Institute, 2009).
The Human Genome Project cracked the secret of the genetic makeup of humans in three ways: it determined the sequence or order of every single base in the human genome; created the maps that clearly indicate specific gene locations of all human chromosomes; and produced linkage maps which show how inherited traits are passed from the parents to daughter cells. This last possibility became the basis for critical medical intervention as it provided empirical evidence for the inheritance of human diseases over generations. With these possibilities, medical researchers have been empowered to seek newer treatment and preventive options for even the diseases that were once known to be incurable (The Bioethics Research Library, 2010).
The Human Genome Project bears potential impacts in the development of newer and effective tools for disease diagnosis. Early and accurate detection of diseases is critical to the management of human disease condition. It is also expected that individualized disease analysis will bring a whole new meaning to preventive medicine where specific medicines are given to a specific individual. Genetic information about patients will also be critical to healthcare providers, nurses, physicians and genetic counselors to determine specific agents which prove to maintain or improve the health of the afflicted individuals. By a broad understanding of the conditions such as schizophrenia, diabetess and heart disease at molecular level will change the current approaches to devising medications which are specifically target the agent causing aberrations and which are effective to specific types of individuals(U.S Department of Energy, 2009).
Perhaps the most powerful medical application though surrounded with a number of ethical issues is the use of information gained from the Human Genome Project in gene therapy (The Bioethics Research Library, 2010). Gene therapy refers to a technique for rectifying defective genes which are responsible for the development of disease conditions such as CFTR gene which is responsible for cystic fibrosis(U.S Department of Energy, 2009).. In gene therapy, the normal gene can be inserted to specific location to the genome in order to replace the defective one. In another approach of gene therapy, abnormal gene may be swapped from the normal one by homologous genes. The abnormal genes upon identification can be repaired by selective reverse mutation and the gene function is restored. The last approach of gene therapy is the alteration of the regulation of a specific gene. Gene regulation determines which genes are turned off and which genes are turned on (U.S Department of Energy, 2009).
In general, the completion of the Human Genome Project marked a complete transformation in the way medical research is conducted. Powerful tools utilizing the information gained from the Human Genome Project have been used in the developing of diagnostic methods and novel drugs in major Biotech companies. While these new interventions such as gene therapy are effective and accurate, ethical issues have often derailed their development. Future direction should be focused on the development of tools which address the ethical, moral and economic issues in the society.
National Human Genome Research Institute (2009). The Human Genome Project completion: frequently asked question. Retrieved August 27, 2010 from, http://www.genome.gov/11006943
The Bioethics Research Library (2010). Human Genome Project. Retrieved August 27, 2010 from, http://bioethics.georgetown.edu/publications/scopenotes/sn17.htm
U.S Department of Energy (2009). Gene therapy. Retrieved August 27, 2010 from, http://www.ornl.gov/sci/techresources/Human_Genome/medicine/genetherapy.shtml
Wellcome Trust Sanger Institute (2010). The Human Genome Project. Retrieved August 27, 2010 from, http://www.sanger.ac.uk/about/history/hgp/