Ethical, Legal and Social Issues (ELSI) in rDNA technology Introduction: Recombinant DNA technology (gene splicing) was

a stunning new scientific tool in the 1970s. It enables scientists to transplant genes from one species into cells of a host organism of a different species. The public, and many scientists, worried that splicing together DNA from different species might create new organisms that would pose fundamental risks to life on our planet. Indeed, in 1973 a group of highly respected scientists, including many of the leading researchers in the field, established a voluntary moratorium (suspension or halt) on classes of experimentation until the risks of gene splicing could be carefully assessed. Subsequently, Chemistry Nobel Laureate Paul Berg of Stanford chaired a committee that considered the issues and established a meeting at the Asilomar Conference Center in California in February 1975. About 140 scientists from 13 countries, including Phil Sharp and David Baltimore of MIT, as well as attorneys, government officials, and members of the press attended. The purpose of this conference was to decide whether to lift the moratorium, and if so to define experimental conditions and protocols for safely conducting gene-splicing work. Indeed the conferees decided that the moratorium should be lifted. They also outlined strict biosafety guidelines that were subsequently adopted by the U.S. National Institutes of Health, and ultimately were adopted in many other countries. These remain the basis of guidelines followed today. Recombinant DNA technology has flourished as a ubiquitous tool in biological research, as the basis of important new drugs, diagnostics, and therapies, and indeed as the basis for the biotechnology industry of which Cambridge and Boston form a major center. In recent years there has been some controversy, especially in Europe, about its application to agriculture and nutrition, but on the whole it is an accepted basis of important and wide ranging scientific, medical, and agricultural endeavors. The use of the recombinant DNA technology now dominates research in biology. It has altered both the way questions are formulated and the way solutions are sought. The isolation of genes from any organism on our planet, alive or dead, is now routine. Furthermore, the construction of new variants of genes, chromosomes, and viruses is standard practice in research laboratories, as is the introduction of genes into microbes,plants, and experimental animals. There are many ethical issues surrounding genetic engineering. We do not know the long term effects of altering genes. Recombinant DNA also gives scientists far greater control over genetic manipulation. Some of the Ethical issues were discussed below: Ethical issues in using r DNA technology in medicine As mentioned earlier, advances in molecular biology have made diagnosis of some of the diseases very sensitive, accurate and rapid. Diagnosis of genetic disorders associated with chromosomal alterations often helps in deciding the course of treatment for the patient. However,

these tests are expensive as they involve costly molecular biology reagents and should be recommended only if it is absolutely essential for patient management and care. Unfortunately, very often, a plethora (excess) of tests is recommended only to recover the cost of the expensive equipment purchased to carry out the test. Drugs such as tissue plasminogen activator, used to break up clots that cause heart attacks and strokes, and erythropoietin and colony-stimulating factors, used to restore blood supplies in cancer patients being treated with chemotherapy, are extremely expensive. Although insurers often cover the costs in the United States, people in many other nations cannot take advantage of these drugs. With the discovery of genes involved in the etiology of various diseases it is now possible to identify those which confer susceptibility to the disease. Individuals carrying the susceptibility gene may be at a higher risk of contracting the disease. On learning that a person is carrying the susceptibility gene, can one stop or prevent progression of the disease? Prophylactic treatment can be given to some such individuals. Environmental factors which trigger the disease could be avoided. Could the knowledge that one is carrying the susceptibility gene lead to more problems than benefits? Will it lead to discrimination in employment, insurance policies, social life? Very often when screening families with familial cancers for susceptibility genes, it is difficult to convince unaffected, young, unmarried females to provide a sample of blood for genetic analysis. They fear that if they were found to carry susceptibility gene/s they would be stigmatised. Such information therefore has to be kept strictly confidential. Informed consent has to be obtained from the participants after explaining the risks and benefits of the research or treatment. Genetic testing presents several ethical challenges. Legislation is in place or is being developed to limit access to genetic information, so that employers or insurers cannot discriminate against individuals because of their genotypes. Testing for a genetic disease presents a complication not seen in other types of illnesses, because the diagnosis of one individual immediately reveals the risk that other family members may be affected, based on the rules of inheritance. For example, a young woman learned that she is a carrier of Wiskott-Aldrich syndrome, which causes severe immune deficiency that is lethal in childhood. Because the mutant gene is carried on the X chromosome, each of her sons faces a 50 percent chance of inheriting the illness. Knowing that the same would be true for other carriers in her family, the young woman chose to inform all of her relatives who might also carry the gene. The decision of whether or not to be tested rests with the individuals. Ethical issues in somatic and germline gene therapy in humans the most deeply felt concern is that genetic research in general and the institution of broadbased genetic testing will spur a malevolent renewal of interest in eugenics. This view stems from the presumption that current attempts to perform gene therapy by modifying the genetic constitution of somatic cells-i.e., the nonreproductive cells of the body a goal that most people find acceptable, will ultimately lead toattempts to alter human germ-line genes-i.e., those passed on to future generations via sperm and eggs. There are technical reasons for believing that the value of such modifications for humans is questionable and, therefore, unnecessary. Indeed, many scientists agree that in the absence of

any evidence of indisputable therapeutic utility and without absolute assurance of complete safety, attempts at human germ-line modification should not even be considered. Somatic cell gene therapy is only a small step forward as the DNA is not passed on to the offspring. The only problem that one envisages from somatic gene therapy for genetic disorders is that this may significantly enhance the proportion of abnormal genes in the population. Individuals with defective genes will be able to survive, reach maturity and pass these genes to their offspring. This can be avoided by introducing the therapeutic DNA into the germline cells. Such genetic manipulations would offer considerable hope to individuals with genetic disorders. However, the technology for germline gene transfer in humans needs to be improved to be sure that abnormal foetuses are not formed due to the manipulations. But the major question is - is it ethical? Are we justified in changing the genetic make- up of a human being? One may argue that it should be permissible to rectify a genetic defect. But would it lead to selecting good genes for physical appearance, intelligence etc? Will there be another Hitler who will try to change the human race with these powerful tools in hand? One of the worst example of a failiure in gene therapy was on 1999 when Jesse Gelsinger, aged 19 died just after 5 days of gene therapy for a rare genetic disease, known as ornithine transcarbamylase (OTC) deficiency, which affected his ability to rid his body of ammonia, a usual, but toxic, breakdown product of protein. Half of children with OTC die in their first month of life, and half die before their fifth birthday. Jesse had a mild form of the disease because some of his enzymes were functioning normally. He was therefore able to control the disease with diet and drugs, though he needed to take 32 pills a day. Wilson and Batshaw worked together to develop the OTC protocol and, in 1995, they submitted it to the National Institute of Healths (NIH) Recombinant DNA Advisory Committee (RAC) and the Food and Drug Administration (FDA) for review and approval, as is required for all human experiments involving gene therapy. The researchers believed that in the worst case, the trial might result in an inflamed liver. On September 13, 1999 Dr. Raper injected 30 milliliters of the adenovirus with the corrective OTC gene into Jesses bloodstream. According to the physicians, Jesses severe immune system reaction led to multiple-organ-system failure and he died on September 17th, 1999, four days after the gene-therapy injection. Medication usually controlled Gelsinger's condition, but he chose to join the clinical trial so that he might help babies who died of a more severe form of the illness. Although Gelsinger clearly stated that he realized he might die, questions arose about the extent of his knowledge, largely because he had been healthy. This issue does not arise in the more common situation in which a participant in a gene therapy trial has exhausted conventional treatments, because he or she has little to lose at that point. Clinical trials of gene therapy are now conducted with much greater care. Human gene therapy experimentation raises many issues. The promise of the technology is represented as very great and the reality of it is very dangerous. Human gene therapy must be seriously and cautiously evaluated. Without increased and more effective oversight, Jesses death could be the first of many in gene therapy. Though Jesses participation in the human trial did not provide him or the infants with OTC with any benefit, it did perhaps lead to something even more important in this field. Jesses death has forced researchers and government officials

to reappraise the current framework and structure of gene therapy research, to reexamine informed consent procedures, and to take public responsibility for their actions.

Cloning of a sheep from an adult cell, closely followed by cloning of a monkey, has caused quite a furore (uproar) worldwide. This technological feat has a tremendous potential in our understanding of genetics and reproduction, in improving the process of breeding where farm animals are considered. Whether this would lead to man making numerous copies of himself/ herself; whether this abnormal way of reproduction should be permitted, are some ethical, moral and spiritual questions. Conclusion The recent advances in biotechnology present both benefits and risks. They have revolutionised the process of drug manufacture, diagnosis and treatment and the production of animal models for human diseases. There is a tremendous potential for creating new drugs and treatment. This technology raises important ethical issues in the social structures including families, preventive medicine, employment, health insurance etc. We must interact with the general public, to educate them, and prepare them better for the impact of biotechnology. The scientific and medical communities and the public, in general, have to use these powerful tools responsibly, for the maximum benefit of mankind.