The human genome consists of 50,000 to 100,000 genes located on 23 pairs of chromosomes. One chromosome in each pair is inherited from the mother, and the other from the father. Each chromosome contains a long molecule of DNA, the molecule of which genes are made. The order of the four bases on the DNA strand determines the information content of a particular gene or piece of DNA. Mapping is the process of determining the position and spacing of genes, or other genetic landmarks, on the chromosomes relative to one another.
The possibility of initiating such a major and significant research program was extensively discussed in the scientific community during 1986 and 1987. In the spring of 1987, a report on the human genome initiative was prepared by the Health and Environmental Research Advisory Committee (HERAC) of the Department of Energy (DOE). In early 1988, further discussion culminated in the publication of two additional, widely circulated, influential reports. The U.S. Congress Office of Technology Assessment (OTA) report presented a comprehensive and detailed analysis of the scientific developments that had led to the promise of "mapping and sequencing" the human genome and presented an outline for a multi-phase research plan for accomplishing the goal of sequencing human DNA over the course of the following two decades. In fiscal year 1988, the Congress of the United States launched the human genome project by appropriating funds to both the DOE and the National Institutes of Health (NIH) specifically for support of research efforts to determine the structure of complex genomes. The NIH was delegated $17.2 million and the DOE received $10.7 million in 1988 by the human genome research institute.
It is generally agreed that the overall goal of the Human Genome Initiative is to acquire fundamental information needed to further our basic scientific understanding of human genetics and of the role of various genes in health and disease. As refined through the discussions over the last half of the 1980's and defined in the NRC report, the Human Genome Initiative has several interrelated goals:
Because of the size of the human genome, the NRC committee and others recommended a multi-phase program. A general plan to eventually produce a human genome map over a five year period was approved by the NRC. The initial pilot phase would consist of the following:
It was decided upon that the task of sequencing the complete human DNA would be taken up at a later date or phase. And this would only be completed if it could be done at a reasonable cost. The overall program was expected to take at least fifteen years to complete. This general plan is still appropriate, but some of the details changed as improvements in the technology occurred.
The international consortium currently includes three U.S. laboratories funded by the NHGRI of the NIH, the joint Genome Institute of the U.S. DOE, and the Sanger Centre supported in the United Kingdom by the Wellcome Trust. In the initial or pilot phase, eight scientific teams supported by NHGRI, DOE and international collaborators completed the sequence of over 480 million bases, of which 260 million (or close to 10 percent of the human genome) are in high-quality finished form. The pilot project also drove down the cost of sequencing to an average of 20 - 30 cents per base today. In 1986, it was estimated that one skilled person could sequence 100,000 base pairs per year at an average cost of $1/base pair. The consortium's goal is to produce a working draft covering at least 90 percent of the human genome sequence within one year or by the spring of 2000, and to have it completely finished by the year 2003. Besides sequencing human DNA, Genome Project researchers are developing new sequencing technologies and conducting studies of human genetic variation, genomic function, and genomic analysis of model organisms. Scientists can use these tools to help them "read" the information coded in the DNA sequence, which will help them understand human illnesses and, ultimately, to find dramatically new treatments and cures. In addition to these goals, the HGP will continue to vigorously support research on ethical, legal, and social implications of genome analysis.
While the mouse genome is not simpler than that of man, it is particularly useful for comparisons because of the many biological similarities between the mouse and man. The genetic map of the mouse, based on morphological markers, has already led to many insights into human genetics. There is every reason to believe that a physical map of the mouse genome will be equally useful so this was one of the early goals of the consortium. The HGP is also carrying out studies on E. coli to help develop the technology and interpret human gene function.
So the major goal of these groups and organizations is to complete a genetic map of the human genome as soon as possible. There are other goals such as the mouse but the most exciting and anticipated one is that of the human genome. There is some competition out in the industry that is why the federal government added substantial amounts of money to this fund. The consortium now projects to have the complete genome mapped by 2003. This information when complete should be available to the general public. With this information scientists and doctors can better treat diseases before they even occur or even after they have appeared in some instances. This information will allow those that are genetically predisposed to certain diseases to eliminate at least the genetic contribution to the diseases. In some cases the genetic contribution is significant to that person having a disease and in others it is not significant.
Here is a list of conditions and diseases associated with genes: Alzheimer's disease, Lou Gehrig's disease, Arthritis, Asthma, Cancers, Cystic fibrosis, Diabetes, Down syndrome, Hemophilia, High blood pressure, Hypercholesterolemia, Multiple sclerosis, Muscular dystrophy, Neurofibromatosis, Schizophrenia, Sickle-cell anemia, Spina bifida, Tay-Sachs disease, and many more. The length of this list gives people an idea of the potential impact of a map of the human genome. Each one of these diseases affects thousands of people and together probably many millions of people. With some of these diseases or conditions such as cancer and high blood pressure, are not solely controlled by genes. For example, a person that receives gene therapy could still get cancer from smoking. So people will still have to exercise and eat right to control blood pressure and reduce other problems.
The fist actual use of gene therapy began in September 1990, with the treatment of a child suffering from a rare genetic immunodeficiency disease caused by the lack of the enzyme adenosine deaminase (ADA). ADA-deficient people have persistent infections and high risk of early cancer, and many die in their first months of life. This young boy was treated with gene therapy and the disease was treated, but the ADA gene-corrected cells have to be re-infused every one or two months. This allowed the young man to lead a somewhat normal life. The minor difficulty of repeat infusions is a small price to pay for a normal life. People with diabetes often have to adjust insulin daily. This is an example of gene therapy, but this could not be done until the scientists knew exactly which gene was causing the problem. When the genomic map is complete, scientists will be able to better cure or aid in the cure of many diseases. As I am writing this I hear on the radio that at John's Hopkins Hospital they have successfully used gene therapy to cure colon cancer. Sometimes difficult to diagnose, hereditary nonpolyposis colorectal cancer (HNPCC) is believed to account for one in six of all colon cancer cases. Individuals who have a hereditary risk for cancer are born with one altered gene. This means that this individual already is one step into the cancer process.
Though scientists had known for years that an altered gene was to blame for this hereditary colon cancer, finding it was tricky for they had few clues as to where, on any of the 23 pairs of chromosomes, the gene might reside. Finally, using tools emerging from the Human Genome project, an international team tracked the gene to a region of chromosomes 2. Ten months later scientists found a second gene on chromosome 3 also involved in HNPCC. Together, these genes account for most cases of this inherited cancer.
A big advantage of using genetic engineering to produce drugs is that it's possible to mass-produce chemicals that might otherwise be difficult and costly to extract, or simply unavailable by conventional means. Another important advantage is that drugs produced in this way are pure and, if made using human genes, fully compatible with use in people. For example, before engineered bacteria were cloned to manufacture human insulin, the main source of this hormone (used to treat diabetes) was the pancreas of cattle of pigs. Although similar to human insulin, animal insulin is not identical and some allergic reactions occured. The human protein produced by bacteria with recombinant DNA, however, has no such effect. As another example, vaccines against disease are traditionally prepared from killed pathogens (disease-causing microbes). They are effective in the vast majority of people, but a small percentage of the population have allergic reactions to vaccines. Genetically engineered vaccines are safer because they contain no living organisms - only the proteins that stimulate the body to develop immunity.
Now that I have wrote about the many benefits of genome mapping and gene therapy, I will mention some of the disadvantages. Should information about an individual's genetic makeup become available to others without that person's knowledge and permission? How can we assure that genetic information does not lead to stigmatization or to discrimination in areas such as insurance or employment? These are just some questions that people raise when talking about the human genome. The significance of questions like these is expressed in the amount of money the consortium is spending on this topic. They are spending 3 to 5 percent of the total annual budget, which is approximately 200 million. This could amount to as much as 10 million dollars annually. I think the long term questions regarding the release of a human genome map are unanswerable. I feel there are so many possible questions or problems that will appear that we can't even imagine until the map is released. How might this affect insurance rates for different people. Will insurance premiums be based on your genetic map? I don't believe that this will ever happen, but I wouldn't say that it would never happen. These are some of the questions being talked about right now.
A complete map of the human genome is kind of scary to me, especially when the government is involved with its production. There are a lot of things that the government does that they don't tell the general public. I don't mean to sound like an anti-government person, but yet I am. I believe that they give me reason to be skeptical of their actions. I also worry in general about what this will do with the general public. For example, some people that can't be cured may feel left out because not all diseases or conditions can be cured. People have also raised questions in the areas of courts, schools, military, and many others. For example, could people be accepted in any situation based on their genetic map? And who controls or owns a persons genetic map, and where will it be stored or kept? Will anyone in the general public be able to access the information on your genetic map? I have read a specific paper where scientists ask whether the sequence of the entire human genome is needed. In other words do we need to know some of the junk DNA of the human genome. Instead I think that only the required or needed information from the human genome should be studied. However, this is my somewhat uneducated opinion. I would not want the responsibility of deciding some of these controversial questions regarding this project. The initial human genome map is not being done on one specific person, but rather on pieces from many people. I hope we stay at this point and don't come up with individual maps for each person. We will have the ability to treat most of our diseases or conditions through genetic therapy. I wonder what will happen when it comes to parents that want to have that perfect child. Some parents may be more interested in the genes of the child rather than the child itself. I am sure that there will be parents that are interested in knowing their unborn childs genes and to have the ability to repair any defects and there will be those parents that don't want to know. These are some concerns I have with the project, but there are numerous possible benefits to this project as well. I have talked to many other people about this project in recent weeks and this is a very interesting and scary subject for many.
In conclusion, the human genome has been a long process worked on by many research scientists at many different locations. The annual cost of the project is about 200 million dollars. This is primarily tax dollars, and there are a couple of private firms working on this project and other similar projects as well. As I have mentioned earlier, I have some doubts about this process. However I did learn more about the human genome and where it is going by preparing this paper. I do have to admit that there can and will be many major benefits from the human genome project. With this data, gene therapy is a possibility, and just to have the information of human DNA will probably be the basis of many future experiments. We will also have a genome map of the house mouse, fruit fly, and other organisms similar to that of the human. This will help scientists make decisions on future research involving the human genome.
This research has to be very exciting to work on. What these scientists are about to unveil will probably be the biggest discovery or project in the first half of the 21st century. I say that reluctantly because the way technology is progressing I think there will be much greater discoveries than that of the human genome in the next century. Even this project has had to updated to the advances made in technology. I would bet that if you had asked the founders of this project if they thought this project might be completed earlier and by two years they probably would have said no. This is a very big discovery and a big boost hopefully for mankind and now I wonder what will be next. I hope this doesn't cause to much trouble with the general public, because right now I know a large percent of the population has no idea how far along this is, and if they did know they probably can't understand it. Maybe the government or some university should be writing more about this. As I mentioned earlier in this paper I heard something about gene therapy at Johns Hopkins University, but I think that is a rare news event. I know it is rare because they are working on it right now, but they maybe should be letting more information out through the news to give people time to adjust or at least think about it. Maybe some organization could offer courses to help the general public understand just what is going on, because when you say that the human genome is nearly fully mapped that means absolutely nothing to a majority of the people. A class such as this class would be great, but it may go a little too far for certain segments of the population. Overall, I say again I just hope that this information is used for disease or conditions curing or aiding in cures only, and that it doesn't cause to many problems amongst the American people.