Ethical Principles in Genetics Research – Anthropology by K.V RAMESH

Autonomy or Respect for Persons : This principle refers to respecting the self-determination of individuals and protecting those persons with diminished autonomy. Informed consent is one way of protecting this principle i.e., rights and voluntary decisions of individuals. For all biomedical research the informed consent of the individual, or legal guardian should be obtained. It protects the individual’s freedom of choice to voluntarily agree/ disagree to participate in research or give samples for genetic testing. Adequate information about the testing is given in a simple and easily understandable language in a document known as the Informed Consent Form with Participant/ Patient Information Sheet.
Beneficence and Non Maleficence : In simple terms it just means doing good and protection from harm. Beneficence involves giving importance to the welfare of persons and providing maximum benefits. On the other hand Non-maleficence refers to preventing from harm or trying to reduce harm and is derived from the traditional medical norm of “do no harm”. The principle of beneficence involves giving highest loyalty to the welfare of people and families with the goal to improve the health of population.
Justice: This principle requires treating persons with fairness. It involves distributing benefits and burdens of health care as fairly as possible in society. Therefore persons should be treated fairly, giving them what they deserve, or are entitled to. Distributing the benefits and the burdens of health care ought to be governed by ethically justified rules such as: to each according to need, to each according to an equal share or opportunity, etc.
Informed Consent: A well informed consent and understood consent is essential part of all genetic testing. The central issue of human research in respect to the individual’s autonomy is achieved by obtaining “Informed consent” from adult individuals who are capable of giving a valid informed consent after they have been provided with complete information regarding the condition and the tests. Those persons who are tested are entitled to receive all information in a way that they can understand what is proposed to be done, they must be made aware of any risk, they must be given time to decide whether or not they would like to participate or withdraw from genetics testing/screening. In addition to this the details about the disorder to be screened and its inheritance pattern, reliability of the screening test and what will be done with the samples should also be explained. Information about the implications of a positive screening test (abnormal) should also be explained. In the case of an individual who is not capable of giving informed consent (for example individuals such as children, mentally challenged persons or prisoners etc), the consent of a legal guardian should be taken. Adequate information about the research given in a simple and easily understandable language in a document known as the Informed Consent Form with Participant/ Patient Information Sheet. Table 2 gives the details of elements that should be given in an informed consent form/ patient information sheet (ICMR Guidelines, 2006) A copy of the participant/patient information sheet should be given to the participant for her/ his record. When the written consent (signature or thumb impression) is not possible due to sensitive nature of the project or the participant is unable to write, then oral consent can be taken after ensuring its documentation by an unrelated witness. However the approval for oral consent has to be taken from an ethics committee beforehand. When human biological material or samples are collected, whether in a research or clinical setting, it is appropriate to ask persons for their consent to future storage and use of their samples.
Vulnerable Participants : Vulnerable individuals are those persons who are unable to give valid and understood consent for e.g., minors, mentally disadvantaged, prisoners, institutionalised individuals, terminally ill, students, subordinates and people who do not speak the language etc. Further there are influences of culture or customs which can make certain communities vulnerable. Even adult women may be incapable of giving informed consent without consulting family members like mother in law or husband. In community research where even if consent of the community leaders or head of family is taken, individual consent of every person is a must. In telling about test results (e.g., carrier status for a recessive disorder; which parent carries a balanced autosomal translocation that has caused a disorder in their child; incidental discovery of non-paternity) and in assisting couples to reach reproductive decisions, professionals should be careful to protect the interests of those who may be vulnerable to harm from a hostile environment. Similarly children, persons of diminished mental capacity, and some other groups may not be in a position to make a decision due to their limited capacities. Such people may be vulnerable to harm because of their position in society and need protection from any potential adverse effects of genetic testing. Minority groups are entitled to respect, to their beliefs, customs or way of thinking even if the medical geneticist disagrees with these views. They should be treated equally with persons whose views are in the majority. They should be provided with due information and be given opportunity to take their own decisions.
Genetic Counselling: Every individual should be provided with complete information and opportunity to make choices regarding one’s health. This is important to the person’s integrity and contributes to psychological well-being. All genetic testing should be accompanied with pre-test counselling (to tell about the nature of tests, what is expected etc) as well as a post test counselling (to explain the results of the testing and its implications). Pretest and post test counseling is an integral part of prenatal diagnosis (Kabra, 2003). In order to help a person to make a valid choice, he/she should be provided with more than one alternative. Only those persons who are qualified and experienced in communicating the meaning of genetic information should undertake genetic counselling.
Risks and Benefits: Any research procedure that exposes a person to any risk should be done only if there is proper justification for doing so and there should be expected benefits of the research. All expected or potential risks as well as benefits should be discussed in detail before participation of the person. Also it is important for you to note that in genetic research, the primary risk may not be physical but rather may be psychosocial and can have effects or implications on other members of the family as well. Genetic testing therefore should be offered when the probability of harm is less and the expected benefits are more. Adequate counseling should be given to participants on the meaning of genetic information they receive.
Pedigree Studies: Pedigrees involve obtaining history of other members of the family of the patient or the proband under investigation. It is an important tool in genetics however it may reveal information about the likelihood of other members of the family being either carriers of genetic deseases or being affected by the disease. Special privacy and confidentiality concerns arise in genetic family studies because of relationship between the participants. It should be kept in mind that within families each person is an individual who has the right to keep the information about himself or herself confidential. Family members are not entitled to know each other’s diagnosis. Other members are secondary subjects and they are not entitled to know about the genetic diseases of other members without appropriate informed consent. Before revealing medical or personal information about individuals to other family members, investigator must obtain consent of the individual to do so. To explain this further I will give you an example: In view of the cultural background of our country where woman is still a vulnerable and exploited participant, revealing information to the husband that his wife is the carrier of balanced chromosomal translocation (leading to recurrent abortions or a genetic syndrome in her child) or that she is a carrier of a single gene causing ‘X’ linked or recessive disease, may lead to grounds for a divorce despite the fact that the husband himself is a carrier of the autosomal recessive disorder. While general principles of counseling require presence of both the spouses, necessary care must be taken not to end up in breaking the families. In view of above concerns appropriate caution may be exercised. We must understand that revealing who else in the family has agreed to participate may lead to breach of confidentiality. Also if there is a patient, out of personal interest s/he may put undue pressure on relatives to enroll in the study which may not be acceptable to other members.
Privacy and Confidentiality: Secure safeguards should be in place for protecting private ‘identifying information’ of participants and maintaining confidentiality of research data. Identifying information comprises of all details like name, date of birth, contact details, and other personal information that can be used to identify an individual and therefore needs to be protected. Adequate care should be taken in keeping genetic records, however participants should be told beforehand regarding the limits to safeguard confidentiality and of the anticipated consequences of breach of confidentiality. If the result of the research is of benefit to the health of the participant, then they should be communicated. Once study is over genetic data should be coded or delinked with clinical details to maintain confidentiality (anonymised). Adequate measures should be in place to restrict access of records to unauthorised persons. It needs to be emphasized that consent for screening or a subsequent confirmatory test does not imply consent to any specific treatment or termination of the pregnancy. Specific consent is required from the affected patient to share his/ her genetic information with family members who may be benefited from it.
Inducement vs Compensation: Individuals who participate in research may need to be duly compensated for their participation. Provisions should be made for adequate compensation to reimburse extra travel expenses, loss of wages, compensation and medical care in case of any injury. However the amounts should be reasonable and should not become undue inducement, i.e., so huge that it becomes the only reason for participation as an extra income and motivation factor for a person to give samples for research. Inducement can be in cash as well as in kind. Making promises for extra services or facilities may induce a person to agree to participate in testing even if it is not of any direct benefit to the person. Such promises for extra payments in cash or kind and the amount of compensation must be seen reviewed and approved by the ethics committees before it is provided to individuals. In case of any injury happens due to participation of a persons in research it is the obligation of the researcher/ physician to provide adequate treatment or compensation to cover the extra costs incurred due to this.
Genetic Screening: Genetic screening implies search in population or individuals who have, or are susceptible to have a serious genetic disease. It also includes persons who, though not at risk themselves, are carriers and therefore at risk of having children with the particular genetic disease. It is essential that screening must be done with specific purpose using validated tests. Genetic screening should be done for conditions if it can be ensured that a suitable treatment/ management of the disease is possible. Depending on nature of the genetic defect that is identified and its pattern of inheritance, siblings and other blood relations as well as existing and future generation/offspring may be affected. Screening of newborns is permissible to detect those genetic diseases like phenylketonuria where serious effects of the disease could be prevented by early intervention such as special diet or treatment. It should not be done when there is no cure or for diseases which manifest later in life. Screening of children should be deferred till the time they are old enough to understand and are able to participate in the decision making process, unless the intervention based on result of the test is likely to be of direct benefit to them at a younger age. Anonymous screening may be conducted on general population in order to establish prevalence of genetic traits/diseases. Anonymous samples means all identifying information about person who has contributed sample is removed and there is no way to know whose sample is it. Left over anonymous blood spots collected for screening newborns for treatable disorders could also be used for this purpose.
DNA Testing: For all kinds of DNA diagnosis the general principles of informed consent, confidentiality and other criteria used for any investigation in genetics should be followed. Since the knowledge in this field is new, and relatively complex, a DNA test must be preceded and followed by appropriate genetic counselling. The laboratories carrying out DNA diagnosis should make adequate provisions to explain fully the nature of testing, implications of results to families. Preferably they should prepare brochures in simple language which can be understood by the persons. Differentiating between clinical practice and research can be difficult in genetics as genetic investigations may extend to other individuals as well as families (Parker, 2004).
Prenatal Testing: It is aimed at detecting presence of abnormalities in the foetus. The foetal sample for examination may be obtained through amniocentesis, chorionic villi sampling, cordocentesis or other biopsies. Foetal cells in maternal circulation can also be used for prenatal testing. Non-invasive methods like ultrasound should be preferred whenever available. Prenatal diagnosis should be performed only for reasons relevant to the health of the foetus or the mother and not to select the sex of the child (in the absence of an X-linked disorder). Prenatal diagnosis can be used to prepare parents for the birth of a child with a disability or they have a choice to go for abortion of affected foetus before 22 weeks of pregnancy. Professionals should recognise the human and economic costs involved in prenatal diagnosis and should limit its use to situations where there is a clear benefit. Many of the centers in tertiary care hospitals or urban centers have now initiated carrier screening for some common genetic ailments. Thalassaemia screening an effective control program is being carried out at the Institute of Immunohaematology, Mumbai, India. More than 14,000 women were screened and carriers identified, followed up and offered prenatal diagnosis (Mohanty et al, 2002). Sex selection, whether for male or female, is very harmful to society since it creates an imbalance in sex ratios. For example you must be aware about the change in the sex ratio in India as commonly pregnancies with girl foetuses are being terminated. The situation is very bad in several states of the country including Delhi, Punjab, Haryana, Rajasthan, Bihar where sex ratio is greatly altered. Concerned with the misuse of genetic tests, particularly for the pre-selection of sex, the Government of India has enacted a law known as “The Prenatal Diagnostic Techniques (Regulation & Prevention of Misuse) Act 1994” amended in 2003 to include the Preconceptual diagnostic techniques also. Pre-implantation DNA diagnosisis also a type of prenatal diagnosis. Same precautions and safeguards should be adopted for this purpose also. Presymptomatic and Susceptibility Testing: Presymptomatic testing (e.g., for Huntington disease) identifies individuals who will develop a genetic disorder later in life. Susceptibility testing (often referred to as ‘predictive testing’) identifies persons who are at increased risk for developing common diseases, such as heart disease, but who may never develop the disease in question. In some cases, presymptomatic testing (e.g., for familial polyposis coli) can lead to prevention of the disorder’s most serious effects (e.g.,by colon surgery to prevent cancer). Susceptibility testing can lead to preventive programmes for heart disease or regular examinations to make possible early diagnosis and treatment (e.g., for breast cancer). In other cases, where successful prevention or treatment are not possible, as in Huntington disease, the major benefit of presymptomatic testing is to provide information for planning one’s life and for deciding whether or not to have children. Pre-morbid diagnosis (diagnosing before appearance of adverse symptoms) in children should not be done for which there is no available intervention. Pre-morbid diagnosis in adults may be carried out with informed consent and appropriate genetic counselling.
Gene Therapy: Somatic cell gene therapy is permissible for the purpose of preventing or treating a serious disease when it is the only therapeutic option. It should be restricted to alleviation of life threatening or seriously disabling genetic disease in individual patients and should not be permitted to change normal human traits. The guidelines and clearance for gene therapy is regulated by the National Bioethics Committee under Department of Biotechnology (DBT) and clearance from the local Institutional ethics committee should be obtained. Safety should be ensured especially because of the possibility of unpredicted consequences of gene insertion. All gene therapy trials should have the provision for long term surveillance. Germ Line Therapy is prohibited at present. Gene Therapy for enhancement of genetic characteristics (so called designer babies) should not be attempted, as long term effects are not understood regarding alterations to genetic machinery of humans. Similarly it would be unethical to use genetic engineering for improvement of intelligence, memory, physical abilities etc. even if specific gene/genes are identified in future. Eugenic Genetic Engineering for selection against personality, character, formation of body organs, fertility, intelligence and physical, mental and emotional characteristics is prohibited (ICMR Ethical Guidelines, 2006).
DNA and Cell-line Banking/ Repository: Human genetic material can be enormously precious and especially if it is regarding rare disorders or is derived from special communities or population groups. This material needs adequate preservation and protection for future use and from potential exploitation. Biobanks/Repositories collect, store, and distribute human biological materials for research purposes. Human biological samples in biobanks include organs, tissues, cells, body fluids or samples like serum, buffy coat, DNA, hair, nails, excreta, sweat, buccal scrapings etc. The samples may be anonymously stored with or without its corresponding clinical information in a database. Appropriate informed consent is needed for long term storage of samples for future testing and research. Issues related to use of samples, their control and ownership, and the benefit sharing to the individuals or community also need discussion. To prevent any exploitation and protect the rights of participants, the three main requirements are individual informed consent for future research, approval of the IEC and the Repository Ethics Committee, wherever applicable.
Cloning : Research using human stem cells to grow new tissues (in order to repair or replace those damaged by disease) holds potential promise. Some of this research may involve nuclear fusion of an adult individual’s cell with an enucleated egg, a first step toward potential human cloning. The possible benefits of research using nuclear fusion to produce tissues for the treatment of disease are recognized, provided that there would be no attempt to reproduce an entire human being. At the present time, “reproductive human cloning” is unsafe and should not be attempted
Stem Cell Research and Therapy : The stem cell research holds a great promise for improving human health by control of degenerative diseases and restoration of damage to organs by various injuries. At the same time it also raises several ethical and social issues such as destruction of human embryos to create human embryonic stem (HES) cell lines, potential for commodification in human tissues and organs, possible use of technology for germ-line engineering and reproductive cloning etc. The research in this field, therefore, needs careful consideration. It is important to protect safety and rights of those donating gametes/ blastocysts/ somatic cells for derivation of stem cells; or fetal tissues/umbilical cord cells/ adult tissue (or cells) for use as stem cells. Safeguards are also needed to protect research participants receiving stem cell transplants, and patients at large from unproven therapies/remedies. Most of the stem cell procedures are still in the research or experimental phase and long term effects are unknown therefore stem cell studies should be done as a clinical trial and not offered as proven therapy to patients.
Commercial Issues, Stigmatisation and Discriminations Based on Genetic Characteristics : When commercial companies are involved in research, it is necessary to protect researchers and participants from possible coercion or inducement to participate in the study. Academic institutions conducting research in alliance with industries or commercial companies require a strong review to probe possible conflicts of interest between scientific responsibilities of researchers and business interests (e.g. ownership or part-ownership of the investigator in the company developing a new product). Prospective participants in research should also be informed of the sponsorship, so that they can be aware of the potential for conflicts of interest and commercial aspects of the research. The other concern is regarding insurance issues where knowing about certain types of genetic information can lead to discrimination by insurance companies who may refuse to provide insurance or charge higher premium. Similarly there is a potential threat that employers may not provide jobs to individuals with certain type of genotypes or school may not admit children based on their genetic diagnosis. There are also major concerns regarding stigmatisation of certain population groups or certain communities based on the genetic information. Many of these examples may sound theoretical today however with emerging new tools for genetic diagnosis there is a need to make provisions in advance for protecting populations or groups from such potential harm. It is need for us to be aware of these scenarios and protect our rich heritage.
Patenting: Biomedical research in human genetics can lead to the development of diagnostic and pharmaceutical products. Patents may be necessary to raise funding to develop such products commercially, but gene sequences without proven utility should not be granted patents. Patenting has the potential to impede international collaboration, especially between developing and developed countries, to the ultimate detriment of service delivery to those with genetic disorders. Genetics differs from many areas of research in that important new knowledge can come from a family, or an ethnic group, with a particular genetic variant. If this leads to the development of a diagnostic test or new therapies, equity requires that the donors, or the community generally, should receive some benefit.
Research in International Collaboration: India with its rich biodiversity and genetic resources, conserved gene pools, indigenous population groups is often an attractive destination for researchers from other countries. However it should not only be provider of samples but be an equal collaborating partner in research to ensure development in science. Such collaborative partnerships should lead to development of capacity within the country for better genetic research rather than mere transfer of samples abroad for diagnostic purposes. At present a lot of genetic research is carried out in International collaboration. This requires adequate care so that the rights of the communities/ persons from whom samples are derived from are adequately protected if there is transfer of biological material across borders. On one hand, collaboration in genetics helps build capacity and is useful for betterment of scientific knowledge but on the other it should not give the impression of experimentation on the population of one country by another. There is a Govt of India notification on “Exchange of Human Biological Material for Biomedical Research” issued on 19.11.97 by Ministry of Health and Family Welfare. Appropriate regulatory clearances are needed for international collaboration and Ethics committee approval has to be taken before the initiation of research.