Bioethics in India: Proceedings of the International Bioethics Workshop in Madras: Biomanagement of Biogeoresources, 16-19 Jan. 1997, University of Madras; Editors: Jayapaul Azariah, Hilda Azariah, & Darryl R.J. Macer, Copyright Eubios Ethics Institute 1997.
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5. Ethical Issues in Molecular Detection of Presymptomatic Genetic Disease, Prenatal Diagnosis and Genetic Manipulation

T. Satesh & Y.R. Ahuja

Genetics Unit, Bhagwan Mahavir Medical Research Centre,
10-1-1, Mahavir Marg, A.C. Guards, Hyderabad 500 004, Andhra Pradesh


Abstract

Progress in molecular biology has enabled us to better understand human genetic disease, and has helped enhance the quality of life. This has been possible with technical developments to detect genetic disease presymptomatically. Presymptomatic testing would not only yield information about the carrier status of an individual but also about other family members. Such information may lead to unreasonable beliefs and could alter social relationships. Ability to gain genetic information of the fetus has reduced the burden of suffering on human beings. Since fetal abortion is a sensitive issue, approach to such an information should be evaluated critically and cautiously. Increase in genetic knowledge and capacity to manipulate life-form for convenience has raised several ethical questions and has challenged our moralistic and traditional responses. In India, little emphasis has been laid on ethical issues regarding genetic testing of disease. With adoption of new technology, it is high time that necessary steps are taken in this direction.

Introduction

Bioethics is a broad term and a very broad field of study. Bioethics can be defined as that discipline dealing with ethical issues raised by new developments in medicine and biological science. In the past (about 50 years ago), bioethics was used to solve simple ethical problems using Hippocrates postulates and Christian humanism. With advances in technology and cultural revolution, the traditional approaches of bioethics fail to account for certain complex events. Bioethics, as a separate formal field of study is roughly around 25 years old and one origin is the 1962 publication of Life magazine (3). Modern approaches to bioethics are derived from disciplines like philosophy, theology, medicine and law. The four cardinal principles that underline bioethics are confidentiality, beneficence, justice and autonomy (4). Medicine and other benefits of science have reached many social, cultural and religiously diverse groups and acceptance of these benefits have triggered wide variety of responses, and has generated good public interest. In such a scenario, bioethics accounts for changes in both understanding and meaning. Application of bioethics involves three players: Physicians to practice beneficence, society to defend justice and patients to be granted autonomy. Many professionals need to be involved to accomplish these goals. A universal bioethical law is the need of the day. We wish to discuss three issues involving bioethics: presymptomatic genetic testing, prenatal diagnosis, and genetic manipulation.

Presymptomatic Genetic Testing

Genetic testing for hereditary susceptibility to disease is new and the possibility of early diagnosis has changed the advent of genetic testing. Presymptomatic molecular diagnosis is important in identifying carriers in populations, which could enable us to stop manifestation of disease prior to its occurrence. Molecular diagnostic tests are available for several diseases, such as Huntington's disease, cystic fibrosis and sickle cell anemia. This has been dubbed as genetic prophecy (5). The information gained by molecular testing could be also misused.. Ethical difficulties due to molecular presymptomatic testing arise at three different levels, in society, in employment and in insurance.

1. Social Issues

Genetic testing may lead to discrimination and stigmatization. In our country, religions have strong hold over us and diseases are considered as punishment to evil deeds committed in the past or previous birth. Marriage is an important institution in our society. Mates are drawn from endogamous populations belonging to the same caste and religion. Individuals affected or carriers would be looked upon by our social system.

At an individual level acceptance to predisposition to a disease is a slow and painful process. The psychodynamics involved are rather complex (6). Another important aspect in the issue whether children should be aware of a disease they are going to suffer from, and particularly one which has no cure. Example of cystic fibrosis would throw more light on this issue. The simplest CF tests can pick up 75% of the carriers. The accuracy of the diagnostic test is important. One fourth of the carrier couples would be missed by this test. This leaves 56% of the carrier couples at risk. If both partners would be identified as negative by this test (7). Genetic screening opens new avenues for carriers and many of these may not be generally accepted by individuals or couples (8). These include: remain childless, by remaining single or voluntarily foregoing the opportunity to have children; Selection of a partner, who is not a carrier; To use assisted reproduction techniques in order to avoid having affected children. Each of the above options have raised controversies and are topics under intense consideration in the West. Acceptance of these would involve personal sensitivities.

Molecular testing can reveal information about relatives of an affected individual, who otherwise may not wish to know about their genetic status of the disease because this may lead to excommunication and discrimination of healthy individuals.

2. Employment

Denial of employment on the basis of information gained by genetic testing, is cause of serious ethical concern. The example of an American firm, which screened black employees for the presence of sickle cell anemia (9) is very apt here. Interest of an employer lies in investing into the expansion of business rather than on equipment for the safety of a specific employee. The better option for the employer is sacking the employee, citing reasons other than genuine. Re-employment might not be possible with a new employer for the same reasons.

3. Insurance

Insurance companies have started to think in a direction where a person predisposed to a particular disease may not be able to have insurance cover. The insurer could go for a test without the knowledge of the customer and basing on the results of the test insurance policy could be sold or withdrawn.

Prenatal Diagnostics

Prenatal diagnosis is the identification of disease of the fetus. The three main purposes of prenatal diagnosis are: to inform and prepare parents for the birth of an affected infant if any; To allow in utero treatment for postnatal treatment, if required; To indicate termination of an affected fetus. As of today, termination of affected fetus dominates over its management (12).

Technology today is capable of detecting a disease/disorders of the fetus to which it is going to be susceptible in the future, from the mother's blood stream. We can well list out many diseases the unborn child is likely to be born with. Information gained from a battery of tests may affect the child in admission to school and college, employment and social standing. Steps to be taken towards proper use of prenatal diagnosis must be taken after careful and deliberate consideration. The fetus and abortion are sensitive issues. Ethical discussion on these topics is exhaustive. Much scholarship has been devoted here and in the West. It has become a major political argument.

Genetic Manipulation

Any significant progress in science has been subjected to close scrutiny. Genetic engineering is at present subjected to many ethical and philosophical questions, such as: How safe is it to tinker with nature and who should be held responsible for such acts against the very fabric of life? Is man justified in manipulating nature? Who should decide what is a safe experiment? A similar dilemma was encountered by atomic scientists half a century ago. Unlike genetics, atomic science was born in quiet academic circles under the cover of war. In the beginning, atomic science was made of abstract equations and none could have anticipated the destruction it has caused. Genetics on the other hand, has come under a wide media coverage and the public interest has been very large. An interesting fact about the ethical aspect of genetic engineering is that, geneticists themselves have sent alarm signals (10).

Whereas genetic technology has created huge expectation and returns, the accomplishments are few. Corporate houses have invested huge sums of capital and are eager to profit from their biotechnological skills. In their enthusiasm to reap quick profits, some important factors may be neglected or overlooked. It is very important to assess these lapses. Dangers can be at two levels: a possible human hazard and possible ecological disruption (11).

1. Human hazard. How safe are those involved in manipulating genomes? The evaluation of risk involved in working with vectors, proper disposal of laboratory by-products and critical evaluation of the manipulated organism is needed.

2. Ecological hazard. Modified organisms can be sources of instability in an ecosystem. The disturbance may be observed after certain damage or it may go unnoticed. For example, recombinant DNA technology has enabled the production of insulin from E.coli strains. These organisms have been grown in large quantities and insulin harvested. Insulin is carefully regulated in the human body, and this equilibrium could be upset in an event such as insulin producing bacteria could gain entry into human intestines, was to occur, this would well mean a man-made disease. The second aspect is ecological hazards of monitored organism, which can be sources of instability in an ecosystem at various levels. Some effects may be beyond human observation. Involvement of intelligentsia is not only required, but the participation of the common man is very much necessary. A consensus should be reached based on ethical questions like, How far are we to proceed and develop genetic engineering? Do we want to assume basic responsibility for life on this planet? Should we take evolution into our hands, which otherwise is a slow process in natural time scale?

Gene therapy is an effective way to correct gene deficiencies by replacing defective gene or supplementing it. Gene therapy is distinct and differs from other medical therapies, because it brings about changes in make up of an individual. Biblical saying goes 'God made man in his own image'. How far is man justified 'playing God', tampering with human genes. Gene therapy seems to be less mired with ethical problems than gene diagnosis. It was first performed in 1990 on adenosine deaminase (ADA) gene in the USA. In India, so far a gene therapy trial has not been reported. There are many unresolved issues to currently available gene therapies such as safety and stability of the vectors, behaviour of the gene after transfection, etc.

Basic considerations concerning gene therapy in India would be (a) To study the validity of the available protocols from abroad and evaluate as to how well they suit Indian conditions. (b) Indigenous development of techniques so as to reach the benefit to millions.

Conclusion

These issues of bioethics seem to have little relevance in India. Being adeveloping country, unemployment, hunger and poverty hold priority. However, bioethical issues should not be ignored. Genetic diseases in India have not drawn much attention and the geneticist is confined to the four walls of the laboratory, unaware of the prevailing situations. On one end of the spectrum it is the liberal, affluent and the educated class whereas on the other illiterate and poor. Of course, there is a sizable middle class too. Taking decisions can affect each of these groups in different ways. Risk and benefits have to be weighed keeping in view all these groups. The study of responses to topics, like prenatal diagnosis and genetics testing, can gather up to provide us with much information.

References
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