and, therefore, their genes are much easier to map. Researchers have mapped the genome sequence of some and fruit flies. Mapping the genes of these simpler organisms can contribute to understanding both how genes are structured and what the function of each gene is. The structure and function of each of these genes is easier to determine than those of human genes.
Mapping the genome of humans has been an immense task. Many scientists worldwide have been involved in the project over ten years at a very high financial cost. The outcome of this project has vast potential - the information gathered will be used as the basis for new research areas in human biology and medicine and will help provide insights into the genetic basis of human disease and inherited disorders (e.g. Huntington’s chorea, Down’s syndrome and cystic fibrosis.)
Genetic (inherited) characteristics are often responsible for diseases, such as the above examples. Analysing the genome makes it possible to spot these potential outcomes and, hopefully, prevent them by using some form of gene therapy. Once scientists understand how these genes contribute to disease, it should be possible to rather than simply treat them. Of course, that would be of enormous benefit to someone with a family history of cystic fibrosis or breast cancer. This is because some genetic defects lead to certain syndromes. These syndromes, eg cystic fibrosis, make the carrier predisposed to certain diseases. Repairing the “faulty” gene, if possible and desirable, may remove this predisposition and, with it, the possible disearse.
There are two main categories of gene-mapping techniques: linkage (or genetic) mapping - a method that identifies only the relative order of genes along a chromosome; and physical mapping - a group of more precise methods that can place genes at specific distances from one another on a chromosome. Both types of mapping use genetic markers, detectable physical or molecular characteristics that differ among individuals and which are passed from one generation to the next.
Linkage mapping was developed in the early 1900s by the American biologist and geneticist Thomas Hunt Morgan. By observing how frequently certain combined characteristics were inherited in numerous generations of fruit flies, he concluded that traits that were often inherited in combination must be associated with genes that were near one another on the chromosome. From his studies, Morgan was able to create a rough map showing the relative order of these associated genes on the chromosomes, and in 1933 he was awarded the Nobel Prize for Physiology or Medicine for his work.
Human linkage maps are created mainly by following inheritance patterns in large families over many generations. Originally, these studies were limited to inherited physical traits that could be observed easily in each family member. Today, however, sophisticated laboratory techniques allow researchers to create more detailed linkage maps by comparing the position of the target gene relative to the order of genetic markers, or specific-known segments of DNA.
Physical mapping determines the physical distance between landmarks on the chromosomes. The most precise physical mapping techniques combine robotics, lasers and computers to measure the distance between genetic markers. For these maps, DNA is extracted from human chromosomes and randomly broken into many pieces. The DNA fragments are then duplicated numerous times in the laboratory so that the resulting identical copies, called clones, can be tested individually for the presence or absence of specific genetic landmarks. Those clones that share several landmarks are likely to come from overlapping segments of the chromosome. The overlapping regions of the clones can then be compared to determine the overall order of the landmarks along the chromosome and the exact sequence in which the cloned pieces of DNA originally existed in the chromosome.
Very detailed physical maps that indicate the precise order of cloned pieces of a chromosome are required to determine the actual sequence of nucleotides. The Human Genome Project most commonly uses the DNA sequencing method developed by the British biochemist and Nobel laureate Frederick Sanger. In Sanger’s method, specific pieces of DNA are replicated and modified so that each ends in a fluorescent form of one of the four nucleotides. In modern automated DNA sequencers, the modified nucleotide at the end of such a chain is detected with a laser, and the exact number of nucleotides in the chain is determined. This information is then combined by computer to reconstruct the sequence of base pairs in the original DNA molecule.
Duplicating DNA accurately and quickly is of critical importance to both mapping and sequencing. Scientists first replicated fragments of human DNA by cloning them in single-celled organisms that divide rapidly, such as bacteria or yeast. This technique can be time consuming and labour-intensive. In the late 1980s, however, a revolutionary method of reproducing DNA, known as the polymerase chain reaction (PCR), came into widespread use. PCR is easily automated and can copy a single molecule of DNA many millions of times in a few hours. In 1993 the American biochemist Kary Mullis was awarded the Nobel Prize for Chemistry for originating this technique.
If and when it becomes possible to identify the function of each gene in the genome it will be possible to identify “faulty” genes. This opens huge ethical and moral dilemmas: who is entitled to receive this information? And for what purpose?
A question may arise around how serious an illness or genetic defect must be to warrant the use of gene therapy? Another will ask whether the technology should be used not to cure, but to enhance performance? Since such therapies will work at the genetic level, we will need to decide whether they should be used on foetuses, on children, or only on adults? Deciding to treat diseases that have effects in childhood will not be questioned. But what about other uses, such as enhancing height or athletic ability, treating late onset diseases such as Alzheimer’s; or creating “designer babies”? These decisions will be more difficult.
Should gene therapy be restricted to only serious diseases? Should it be used to enhance traits or characteristics such as memory or intelligence? Maybe the most important question is whether gene therapy should be used on eggs and sperm to prevent any diseases from developing before the baby is born.
There is great promise in a technology that not only can treat disease but also can permanently cure it at the level of our genes. However, it is difficult to undo genetic changes, especially when they may persist many generations into the future. So we must think not only about how gene therapy will affect us personally, but also about our future descendents who may inherit our gene mutation.
Society will derive the greatest benefit from knowledge of the human genome only if it takes measures to prevent abuses, such as invasions of the privacy of an individual's genetic background by employers, insurers, or government agencies or discrimination based on genetic grounds. For example, somebody carrying cystic fibrosis will have a comparatively short life expectancy; should, therefore, their life assurer and/or employer be informed of this fact?
Society must take into consideration possible psychological impact and stigmatisation due to an individual's genetic differences. Also, clinical issues including the education of doctors and other health service providers, patients, and the general public in genetic capabilities will need to be addressed if gene therapy is to work without social risks.
Overall standards and quality-control measures in testing procedures for gene therapy are another important factor to consider, since rich and powerful people can induce unscrupulous practitioners to do with this tool things that it was not meant for – eg cloning themselves, or choosing the characteristics of their offspring. The regulation of this practice ( gene therapy ) is done by national governments after wide consultations with the different sectors of the public about what is and what is not morally acceptable.
Even with these regulations, some people still fear that the rich will benefit more from this new technology than the poor because this therapy may not be available on the NHS. If this were to happen, the gap between those who can afford this treatment and those who can’t will widen.
Some people, because of their own deeply held religious beliefs, do not approve of changing any constituent in the human body. They feel that God has made us the way we are and it is none of anybody else’s business to tamper with it. Some religious groups, like Jehovah’s Witnesses, object even to blood transfusion. Gene therapy, clearly, changes the patient’s physiological structure and renders him/her different from the way God meant them to look like. Catholics, eg, believe that life begins at conception and any interference with the foetus is incompatible with God’s wishes.
Another issue, which borders both the religious and moral aspects, is that of life expectancy. Is it right for us to extend our life expectancy and thus put further pressure on Earth’s limited resources? Is it right for us to postpone death forever?
In conclusion, identifying the genetic code has great promise. It can help us discover causes of disease and better understand who we are. We must recognize, however, that with such promise comes great risk. Even if we would like to know what future our genes hold, the question we must ask is whether that information should be collected, and more important, who should be able to see and use it.
Only a few of the genetic tests now available actually predict whether a person will contract a disease or condition. Instead, most tests offer much more limited information about how much more likely a person is to develop a disease compared to someone who tests "normal."
This kind of information is not very useful for individuals, who would like to know whether they actually have or will get a particular disease, and what steps, if any, they ought to take to protect their health.
But probabilities are very useful for predicting how many people in a group will contract cancer or Alzheimer's disease, and so insurance companies and potential employers may well be very interested in measuring their risks using genetic tests.
The genetic codes that will be used in tests to predict health risks often are, and will continue to be first identified by research on particular groups.
And when we are able to change the future through the alteration of our very genes, the challenge is to think not only for ourselves, but also about how our decisions will affect those who come after us.
Finally, the genome project was carried out mostly in publicly-funded research institutions. However, some of it was done in private laboratories. These labs have registered as patents the sequences they have discovered. One of the questions that future researchers have to face is that of royalties to be paid if any research is to be undertaken on any of the patented sequences. It seems that some understanding has been reached but the question of intellectual rights is another problem to be considered if there are not enough already.