Human DNA is naturally intriguing concept, and the Human Genome Project, HGP which according to Wikipedia is the planet’s largest joint biological program aims at creating a complete and accurate sequence of the 3 billion DNA base pairs that make up the human genome i.e. determining the order of occurrence of base pairs in the DNA segment and to find all of the estimated 20,000 to 25,000 human genes. The database of DNA sequences is available to everyone through the internet. The goal of the project is to determine the chemical base pair sequences which compose the DNA and to identify the genes that human genome contains.
The HGP was proposed and funded by the US government. Other research centers and agencies from the UK, Germany, Japan, France, and China contributed towards the sequencing. The planning of the project started in 1980’s, and initially tried to map the nucleotides which are present in the human genome. In more formal words, the goal can be summarized as “produce a sequence [that] contains the genetic code that sits at the core of every one of the ten trillion cells in each human being”. In addition to it, the project also developed tools to understand and analyze data. This project has allowed us to begin to understand the procedure for building a person. Which can have a major impact on medicine and life sciences.
Even though significant progress has been made, the project is claimed to be completed in 2003, two years ahead of the schedule, however these are just estimates. These advances have only been possible because of the help of evolution of technology. With faster and state-of-the-art supercomputers, recording these sequences has become an easier task for scientists in the modern century.
The Human Genome Project was a large project and required a lot of resources, however if there are results to show, then the investment was and is justified. This project basically provides a manual for the building and maintenance of human body. The genetic advances through this project can have impact on individuals and society, so exploring the consequences of it is also part of the project, under their Ethical, Legal, and Social Implications (ELSI) program. Through this paper, I would like to justify the running of the Human Genome Project through some case studies as well showing the other side of the debate. I personally would like to see more of new discoveries through this project because this is a unique effort and holds a lot of potential for the future.
Technologies and Investments
To successfully be able to understand and analyze high level, complex DNA molecules the HGP needed advanced DNA technologies. This was a generalized requirement and required decent amount of funding for it to be successful. At the time, there was a lot of speculation regarding the project and a debate started. To improve its sustained effort and to improve our ability to analyze complex DNA molecules advanced DNA technologies are required.
As mentioned before, essential technologies were needed for the success of the Human Genome Project, which otherwise would have slowed the progress of the project. BAC (Bacterial artificial chromosome) cloning which paved the way for creating molecular maps, Fluorescence in situ hybridization (FISH) which was used to map library clones to specific chromosomal regions, CTAB-DNA precipitation method which allowed preparation of template DNA from phagemids, phages and plasmids on a small scale which are suitable for human DNA sequencing, A-DNA sequencer which is a completely automated sequencer, and Autoradiography which allowed sequenced DNA segments to be visible for further study. All these technologies and innovations created a lot of progress in the project but required many resources and the cost of those resources will only be justified if the Human genome project lives up to it’s expectations. This rapid upward curve in the innovation of such technologies has led to survival of the HGP as it produced much better results, met it’s promised deadline with much more ease, and produced many success stories.
The main reason for the successful completion of the Human Genome was that it allowed investments and help from the researchers and collaborators all over the world moving beyond the borders in an effort to understand the heritage of our molecules and also to benefit from the techniques and approaches provided by researchers all over the world.
The HGP is a project undoubtedly of high demands in terms of resources. This was known from the start but as better technologies have come in, the HGP has shown more and more potential. However, from an ethical point of view, many critics even today have cracked down on the project. The main reason for this been the timeline of the project and the expenses that go with it. This has led to some modifications towards the plan of the project. Since, the original proposal was to sequence the whole human genome, this has been modified to only mapping of the genome instead of sequencing of the genome. Now, the priority for sequencing the genome has been notably reduced, and the efforts toward it will only be increased if more money comes in for the research. This unimportance is primarily for the non-coding regions for which sequencing may not so worthwhile, and this makes up 95% of the human genome. Another argument against the HGP is that the funding of such large scale projects diverts the resources from individuals who may be able to work on this more efficiently. This graph is showing the funding towards the HGP till 2002.
Though it was estimated by the US government that the project would cost 3 billion dollars, but due to other investments and the techniques it costed 2.7 billion dollars for the U.S government.
However, in my opinion this argument is not very strong as it has been seen in the past that more coordinated efforts have lead to better results, and in this case the efforts are definitely needed on a large scale because of the task at hand.
The HGP has also been linked with some cloning projects and similar research. This is a negative possibility of this project. I would judge this as negative not because of who is cloning or how it is being done but cloning itself is unethical. Human clones would lose their individuality and become artifacts. It could end the natural inclinations of human life. Another similar plan of the HGP is to alter the reproduction method of humans, i.e. parents would be able to design and choose the characteristics of their children. This will interrupt the natural tendencies of life and will not separate us from bacterial reproduction, which is known as asexual. The birth of a child is known as a miracle to humans and if that is taken away from the race, it will leave much less to believe in. However, it should also be noted that cloning can be controlled through proper legislation and it is not the primary focus of the HGP.
Even though, the project has been faced with some debatable criticism, it has some astounding positives which keep the program running. One such positive is that the HGP is a successful business, which may sound odd when describing a science project but the sheer scale of it allows this description. The project has had a great business achievement since more than eight hundred billion dollars have been created because of the project and more than four million people have also been put to work. This is definitely a point which is making a huge positive influence.
There were also claims that whose DNA would be used for sequencing as part of the project and how would their identity be protected. The DNA of volunteers were used whose identity is not disclosed, and the volunteers responded through advertisements they were not called by giving a bribe or forcefully.
The main reason the Human Genome Project continued is to help create medical discoveries which will in turn help people tackle diseases in a more preventive manner and it also helped to get a human sequence. Many illnesses have been better understood and treated with the help of the research provided by the HGP. There are certain groups that are more likely to develop cancer and such diseases, and if we have such information about these groups then we can work towards helping those groups by preventing the diseases in the future.
For example a case study, sickle cell mutation in the genes is one such case. In central africa, people have been exposed to malaria for a long time. This mutation is more common in that population compared to other parts of the world which has been a reason for their vulnerability. The HGP has made an important finding of gene pfap2-g. We know that proteins are essential for cellular function. The order of the bases of the genes in the DNA determine how the protein will look. A mutated gene could lead to abnormal proteins and hence genetic diseases. Now, malaria is caused by the transmissions of a parasite named Falciparum. The pfap2-g gene and PfAP2-G protein are responsible for giving targets to the parasite which allow it develop into gametocytes. This information allowed the HGP to determine the importance of this gene. According to Pietre Carrier, targeting production of gametocytes by decreasing the number of PfAP2-G proteins in merozoites is a possible approach for the future. Another way to reduce the transmission of malaria parasites is to decrease the formation of the protein PfAP2-G, which can be achieved by lowering the transcription of the corresponding gene. So, to decrease the formation of PfAP2-G proteins in malaria patients by minimizing the transcription of the pfap2-g gene, the transmission can be minimized.
Also, certain genes can be more effectively tackled with the correct drug use. This drug modification can be done with the better understanding of the genome which is the main aim of the HGP. Thus, allowing scientists to develop specialized drugs for specific genes which can handle the task at hand more effectively. These advantages of the HGP definitely outweigh the concerns associated with it.
Another interesting case study is of the HGSC, Human Genome Sequencing Center at the Baylor College of Medicine. The HGSC found a rare mutation in baby twins. They were showing neuromuscular symptoms and it was a very dangerous situation for the babies.
At first, the group was able to identify three genomic sequences with the help of genomic sequencing, and later limited the affected gene to just one. This gene was destabilizing 3 neurotransmitter. The name of the gene was sepiapterin reductase. The HGP has thus shown great advancement in the treatment of rare diseases. The symptoms of twins were easily treated because now the cause was known and the discovery of the HGSC led to a successful story of the Human genome project.
Today, with the completion of Human Genome Project, we have a complete sequence of Human DNA, i.e now we have a manual set to know how the human body is made. This makes the start of new medical discoveries to cure the diseases. The genome sequence can be accessed by anyone and this project also made people to unite from different parts of the world.
Even Nobel Laureate, James Watson, who was the first director of the HGP at first thought the Human Genome Project was a waste of money because he thought that first this project should be implemented on bacteria first instead of humans and this was too big a leap. However, he quickly changed his mind as he realized that improvement in genetic maps would lead to better isolation of genes which were responsible for certain diseases. This was an important reason for the initiation of the HGP and the project has clearly grown since. Given the example of James Watson, many critics who have bashed the Human Genome Project are also susceptible to change in their opinion once they see the positives and the results produced by the HGP.
As for the negatives, I have quoted a paragraph from the book (Mapping and Sequencing the human genome, 1988), “A project of this type need not threaten the existing biological research community for several reasons. First, the money ought not be provided at the expense of currently funded biological research. Second, it ought to be distributed by peer review. Third, by including selected other organisms required for the interpretation of the human genome map and sequence, the project ought not mislead the public into placing a false emphasis on the uniqueness of human materials for understanding ourselves. Fourth, this project ought to include work by both small research laboratories and large multidisciplinary centers formed by juxtaposing several small research groups having different expertise.” The entire quote is very important as it itself addresses most of the criticism which has been faced by the project. This was written at the initiation of the project in 1988 and many have forgotten this and they should realize that the HGP committee itself realized these problems with the project and was willing to work towards solving them.
The HGP has improved the speed of research in the field of DNA and hence allowed the discovery of a gene which may be responsible for the eradication of malaria. However, this is just one such case study of promise shown by the HGP. This success story will be fully complete once this leads the retreat of the disease in the future. Also, the story of the twins and genome sequencing helped them fight their symptoms tells about the potential the HGP has to treat rare diseases. Now, with the completion of sequence we have a deeper understanding of how humans came to exist and their evolution. Many projects and research have started after it.
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