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
10-1-1, Mahavir Marg, A.C. Guards, Hyderabad 500 004, Andhra Pradesh
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.
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
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.
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 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.
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
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.
1. Encyclopedia Britannia 'Ethics' p. 6474
2. Cruz Coke R (1995). Introduction to bioethics in contemporary medicine. Rev-Med.-Chile. I 23(3);363-7
3. Jonsen AR (1993) ' The Birth of Bioethics'. Hasting Center Report. Vol. 23-16.p.S1-S4
4. Knoppers BM. & Chadwick R. (1994) The Human Genome Project: under an international ethical microscope.Science265: 2035-6.
5. Wexler NS The oracle of DNA. In Rowland,L.B.Wood,D.S.Schon,E.S. and Di Mauro,S.eds, Molecular genetics in disease of brian nerve and muscle; Oxford University Press.New York.
6. Karl K M (1995) Psychosocial and ethical implications of defining genetic risk for cancers.Annls-NY-Acad-Sci.768.41-52.
7. Wilford,B.S.and Fost N(1990).The cystic fibrosis gene: medical and social implications for heterozygote detection .JAMA.263,2777-2783.
8. Bewley,Susan.(1994) "Ethical issues in prenatal diagnosis" in Abramsky,L. & Chapples, J.eds, Prenatal diagnosis.The human side. Chapman and Hall. London.
9. Servero,R. Screening of blacks by Du Pont sharpens debate on genetic tests. New York Times. (4 Feb 1980), 1.
10. Berg,P.,et al Science, 185 (1974),1417.
11. Robin Richard.(1974) Ethical and social aspects of experimental gene manipulation. In Ethics of Human gene manipulation arranged by the Biophysical Society Ethics Committee, presented at the Biochemistry/Biophysics, Meeting, Minneapolis, M.N. June 4.
12. Chapple, Jean. (1994) Screening Issues - the public health aspect. In Abramsky l. & Chapple J. eds, Prenatal diagnosis the human side. Chapman Hall. London.
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