Genetic research involving children raises special ethical and legal issues that do not arise in the context of adults and genetic research. These are related to capacity to consent to participate in research, the evaluation of research risks and benefits, confidentiality, and the return of results. The issues surrounding the conservation and secondary use of genetic information (for example, through the creation of biobanks) as well as those concerning the familial implications of genetic information also apply to children.

Research involving children is important because children are not merely small adults; they are both physiologically and psychologically different. Disease expression and reaction to treatments are influenced by children’s developmental stages, such that research performed on adults may lead to little or no known health benefit for children. Moreover, many diseases only affect children. With these diseases, children’s involvement in research is an absolute necessity for understanding disease pathophysiology and for the development of new treatments.

However, because children are unable to consent to participate in research, specific conditions must apply to genetic research involving children. The four conditions that must be met are the following: 

• The research could not be carried out in an adult population;
• The research has a direct benefit for the child or for the health of other children belonging to the same group (i.e. with the same medical condition or in the same age group). In cases where the research does not directly benefit the child, it must not expose the child to undue risk or harm;
• The child’s legal representative(s) have given free and informed consent to the child’s participation in the research;
• To the extent that a child is able to understand the nature and consequences of the research, his/her views on participating (also called "assent") must be taken into consideration according to his/her age, degree of comprehension and level of maturity.

• The Universal Declaration on Bioethics and Human Rights (UNESCO, 2005) provides specific guidelines for the involvement of ‘persons without the capacity to consent’, such as children. It addresses issues of consent, assent and the assessment of risks and benefits.
• The 25 Recommendations on the Ethical, Legal and Social Implications of Genetic Testing (European Commission, 2004) requires that children’s interests be considered prior to participation in research and outlines some specific considerations.
• The Declaration of Helsinki (WMA, 2008) also contains provisions to protect ‘legally incompetent’ persons such as children, and addresses issues of consent, assent and the assessment of risks and benefits.
• The International Ethical Guidelines for Biomedical Research Involving Human Subjects (CIOMS, 2002) provides specific guidelines for the involvement of children in research. These guidelines provide criteria that must be met for child inclusion in research and address the issues of consent, assent and the assessment of risks and benefits.
• The Universal Declaration on the Human Genome and Human Rights (IBC UNESCO, 1997) sets conditions for the participation of minors in genetic research.
• The Convention on Human Rights and Biomedicine (Council of Europe, 1997) addresses the ‘protection of persons not able to consent’ with regards to consent, assent and the assessment of risks and benefits.
• In its Ethical Issues with Genetic Testing in Pediatrics, the American Academy of Pediatrics mentions predisposition genetic testing in research involving children and states that such research requires informed consent and recommends pre- and post-test counseling.

There are two types of genetic tests:

• Diagnostic tests are carried out to detect variations on one or numerous genes, in order to confirm or rule out a diagnosis. They are used in clinical health care settings when symptoms of genetic disease are already present.
• Predictive tests aim to identify a genetic mutation in an individual who does not yet show any symptoms associated with a genetic mutation. They can be divided into three categories:
• Presymptomatic tests are carried out on individuals who do not show any symptoms of a disease to determine whether they have a genetic mutation that will trigger the development of a disease with a genetic origin. Although such tests can indicate whether or not a person will be affected by a genetic disease, at some time in the future, the specific time of disease onset and its severity will remain uncertain.
• Susceptibility tests are carried out to identify people who, in spite of being healthy, carry a genetic mutation that increases the risk of developing a disease that is caused by both genetic and non-genetic factors. The development of such diseases (e.g. cancer or cardio-vascular disease) is influenced by multiple genes, as well as environmental factors. Therefore, although susceptibility testing can indicate increased susceptibility to the development of a genetic disease over the general population, this kind of testing does not indicate whether a person will definitely develop the genetic disease associated with the mutation.
• Carrier detection tests aim to identify people who carry a recessive gene with a mutation that is associated with a genetic disease. Individuals identified as carriers will never develop the disease themselves. However, carriers could have children who are healthy (that is, neither carriers nor affected by the disease), carry the mutation without being affected by the disease, or who are affected by the disease.

It is possible to perform genetic tests at all stages of life, from the embryonic stage to adulthood:

• During in vitro fertilization, preimplantation genetic testing can be carried out on the in vitro embryo before transferring the embryo to the uterus;
• During pregnancy, prenatal genetic testing can be carried out to monitor the health of the developing fetus and of the mother;
• At birth, some genetic tests are performed systematically, as part of pediatric care. This is known as newborn screening and it is carried out on all newborn babies born in the majority of industrialized nations. In Quebec, the fees for these services are covered by the Minister of Health and Social Services. Therefore, all newborns in Quebec have a blood sample taken from their heel and collected on filter paper. The tests conducted on these samples enable the identification and rapid treatment of children affected by or at risk of developing tyrosinemia, phenylcetonuria, and congenital hypothyroidia. These diseases could cause death or irreversible lesions if not treated immediately. Parents are also encouraged to send a urine sample from their child (at 21 days old) to a laboratory for screening of more than 15 hereditary metabolic diseases;
• During childhood as well as in adulthood, diagnostic genetic testing can be carried out in order to confirm or rule out a diagnosis;
• Finally, predictive genetic testing (presymptomatic testing, susceptibility testing, carrier detection testing) are generally available only to adult populations. In rare cases, these kinds of tests are used to test minors; such as when predictive testing will allow preventative measures to be taken that will benefit the child’s health. For example, predictive testing is used to identify children who are carriers of a genetic anomaly that predisposes them to developing a type of colon cancer. This type of cancer normally develops before a child reaches maturity, and the identification of at-risk children allows for the integration of periodic follow-ups, premature treatment and the reduction of morbidity and mortality. In these cases, the appeal to predictive genetic testing is that it is in the best interest of the child.

• The Tri-Council Policy Statement (CIHR, SSHRC, NSERC, 1998, 2000, 2005) outlines three conditions to be met for children to be involved in research. It also states that those who are not competent to consent shall not be excluded from research that could be beneficial to them or to the group they represent. The statement addresses the general issues of consent, assent and the assessment of risks and benefits.
• The Guidance for Industry: Clinical Investigation for Medicinal Products in the Pediatric Population (Health Canada, 2003) establishes guidelines for recruitment, consent and assent, risk and distress.
• In Guidelines for Genetic Testing of Healthy Children (addendum) (2009), the Canadian Paediatric Society and the Canadian College of Medical Geneticists released a joint statement that includes a recommendation for genetic research testing with children.

• The Civil Code of Quebec (Art. 21) states that “A minor who is incapable of giving consent may not be submitted to an experiment if the experiment involves serious risk to his health or, if he objects upon understanding the nature and consequences of the experiment.” It adds that a minor may only be submitted to an experiment if it has the potential to benefit his or her health or that of the group to which he or she belongs. Finally, the Civil Code states that consent must be sought from the person having parental authority or a legal representative.

Therapeutic cloning may be of great interest in the creation of embryonic stem cells for research and therapy. It could lead to the production of tissues for potential transplantation or replacement of defective or dead cells. The cells composing a cloned embryo are immunologically compatible with the adult cell donor. It is thus possible to extract stem cells from a cloned embryo and graft them on the donor without the risk of graft rejection. This procedure is currently used to treat burn victims.

Another use for therapeutic cloning is to test new drugs and treatment strategies. Indeed, cloned cells or animals present the advantage of uniformity of drug response.

Finally, reproductive cloning could be a solution available for sterile or homosexual couples wanting to have genetically related children.

In law, informed consent requires the ability to fully understand the nature of a research project as well as the consequences of participating in research. Because children’s decision-making capacity is less developed, they are considered legally incompetent to understand all the relevant aspects of participation in research required in order to provide their informed consent. Therefore, a child’s parent or legal guardian must provide consent for the child’s participation in research.

• The Civil Code of Quebec devotes several articles to human experimentation. Article 20 states that “an adult, capable of consenting, may take part in an experiment as long as the risk involved is proportionate with the benefits that can be reasonably expected.” The situation is different for minors or incompetent adults and is dealt with in Article 21. In addition, Article 22 states that consent must be obtained for research that requires the use of a person’s body part (such as tissue or blood), collected during care. Finally, Article 24 requires that consent to participate in research must be given in writing.
• Certain Quebec laws, having as a goal the protection of the confidentiality of personal and medical information, also deal with research in general and genetic data (Act Respecting the Protection of Personal Information in the Private Sector, Act Respecting Access to Documents held by Public Bodies and the Protection of Personal Information).
• The ‘Plan d’action ministériel en éthique de la recherche et en intégrité scientifique’ (1998) by the Minister of Health and Social Services proposes measures that apply to all establishments of the health and social services network that are taking part in research activities.
• The Guide d'éthique de la recherche et d'intégrité scientifique (2003) by the ‘Fonds de recherche en santé du Québec’ (FRSQ) pertains to research carried out in institutions or by researchers who are funded by this organisation.
• The Quebec 'Réseau de Médecine Génétique Appliquée' (RMGA) has developed two position statements specifically addressing issues surrounding human genetic research (Statement of Principles: Human Genome Research (2000) and Statement of Principles for Genetic Research Involving Children (2007)). These statements constitute non-binding guidelines, but often serve as a reference for ethics committees.

A number of normative international documents address genetic screening. Key documents are highlighted below:

• The World Health Organization (WHO), in its report entitled Medical Genetic Services in Developing Countries (2006), states that genetic screening programs must be supported by public education measures and genetic counseling. Furthermore, decisions concerning participation in these programs must be voluntary and informed.
• In its Report on the Control of Genetic Diseases (2005), the WHO specifies that genetic screening programs must be supported by statutory structures, allowing people to make informed decisions and to ensure that they are protected against all forms of discrimination related to test results.
• The WHO also has a more specific report dealing with genetic screening for sickle-cell anaemia (Report by the secretariat of WHO: Sickle-cell anaemia, 2006). This report recommends, among other things, that sickle-cell anaemia should be screened for at birth, by way of newborn screening programs.
• The World Medical Association (WMA) Statement on Genetics and Medicine (2005, amended 2009) states that the results of genetic screening must be strictly confidential and must not be revealed to third parties (e.g. employers or insurance companies) without the testee’s consent.
• Concerning newborn genetic screening, the International Society for Neonatal Screening (ISNS) recommends that routine screening be conducted when: 1) there is a direct benefit for the child, if the disease is rapidly diagnosed; 2) benefits are reasonably balanced with regard to the costs associated with screening; 3) a reliable test exists; and 4) an appropriate system consisting of testing, genetic counseling, treatment and follow-up is in place. The ISNS also underlines the importance of public education (ISNS General Guidelines for Neonatal Screening, 2002).
• In the context of genetic screening for employment, it is held that this practice impinges on human rights and that current scientific knowledge in this domain is not sufficient to justify its use with a view to health promotion in the workplace (International Labour Organization (ILO), Technical and Ethical Guidelines for Workers' Health Surveillance (1998)).

Assent is an expression of a child’s willingness to participate in research. Dissent, on the other hand, is a child’s refusal to participate in a research project. Although children are not legally competent to consent to participate in research, it is generally recognized that respect for their evolving autonomy requires researchers to obtain their assent. To obtain assent from a child, the nature and the consequences of research should be communicated to him or her in a way that is adapted to the child’s language, comprehension, and maturity level. Some argue that a child’s dissent should override a parent or guardian’s consent to participate in research.

When recruiting children to participate in genetic research, researchers must ensure that the potential benefits and risks of the research are reasonably balanced. When direct benefits for the child participant may be expected from research, the risks must be justified in relation to these expected benefits for the individual participant. However, there is a limit to the risks that children can be subjected to in research: children may not be subjected to research that involves a serious risk to health.

Research that does not hold the prospect of direct benefit for child research participants must hold prospect of benefits to persons in the same age category or having the same disease or handicap as participants. The risk to which the child may be exposed should be minimal or similar to the risk associated with his/her medical or psychological condition.

In Canada, there are no legal rules specifically addressing genetic screening. However, certain Canadian organizations have created recommendations in this area.

• For example, the Society of Obstetricians and Gynaecologists of Canada has guidelines on specific subjects, such as Prenatal Screening for Foetal Aneuploidy (2007). According to these guidelines, screening programs should include a non-directive genetic counseling service and respect patient choices to either accept or refuse all options or screening offered to them at any time during the process. Another example is the Carrier Screening for Genetic Disorders in Individuals of Ashkenazi Jewish Descent, which establishes the criteria for the implementation of a carrier screening program.
• The Canadian Paediatric Society has created Guidelines for Genetic Testing of Healthy Children (2003). These state that the child’s best interests should be the primary consideration in undergoing screening. Furthermore, in all situations involving genetic screening in healthy children, the short-term medical benefits for the child should be the main justification, and parents should be informed of the potential psychological and social risks of screening. In cases of genetic pathologies that reveal themselves in adulthood (revealed in susceptibility screening or predictive screening), screening should not be conducted until the child is able to decide whether he or she wishes to obtain such information. As for determining carrier status, which has primary relevance in the context of reproductive decision-making, such screening should be discouraged in children until they are able to completely take part in the decision of whether or not to undergo such testing.
• Finally, Health Canada created a document dealing with Selected Legal Issues in Genetic Testing: Guidance from Human Rights (2001), which explores confidentiality, protection of privacy, discrimination, participation, and public information in the context of genetic screening.

Research participants have the right to be informed of general research results. At times, they may also receive personal results. Where individual research results exist, those results are disclosed to the child’s parents or legal guardian, who then decide whether it is in the best interest of the child that he or she be informed as well. This decision is made based on the child’s age, development, and maturity level.

The right to confidentiality of research, testing and screening results is exercised by their parents or legal guardians. Results are returned to the child’s parents.

Children’s individualized research results and genetic testing and screening results are disclosed to their legal parents or guardians. However, Article 14 of the Civil Code of Quebec allows minors 14 years of age and older to consent to medical care and so the results of genetic testing and screening carried out for the purpose of medical treatment for children of this age will be disclosed only to the child tested. In contrast, for participation in research, the age of consent is 18 in Quebec (Art. 20 CcQ) and so the research results of adolescent participants will be shared with those exercising parental authority.

When pharmacogenomic research involves children, certain ethical issues must be underlined.

Parental consent to pharmacogenomic research and children’s assent can be complicated due to the complexity of the information that needs to be transmitted. The complexity of this type of research can make explaining information to children difficult. Ultimately, this could affect their assent to participate in research.

Communicating results to children raises some questions such as: who should receive the results (the child, his/her legal representative, his/her doctor, or someone else?) and in what manner? These questions are particularly important because the information could have an impact on a child’s clinical care. They could also have an impact on the family. Should the information be provided to the child’s parents? When a child is mature, should the results be communicated to them? This could lead to problems around communication of results because the child may have forgotten that he/she participated in the research or may no longer be a minor.

Pharmacogenomic research in children could lead to the formation of a new orphan disease group. This would occur where pharmaceutical companies fail to develop pharmacogenomic treatments for children because developing these treatments for only a small group would be an economic disincentive. As a result, children would not benefit from the promise of pharmacogenomic developments. American and European legislation has put provisions in place in the hope of promoting treatment development for children and orphan disease groups.

Some argue that the main problem with cloning is the creation of human beings for specific purposes (for example, to have spare organs, etc.). As the WHO points out in A dozen questions (and answers) on human cloning, there is a risk “that people exist to serve purposes set by other people” or to turn humans into manufactured objects.

Others fear the consequences of the possibility of “bringing the dead back to life” and replacing deceased children or loved ones using cloning. This does not take into account the fact that people are not self programmed by genes. Environmental factors also influence development.

Finally, cloning techniques require a large number of eggs to create a single viable clone. Some see this as posing a risk in terms of the potential exploitation of women and the commercialization or industrialization of human procreation.

Generally, consent is necessary before proceeding with a genetic test or genetic screening.

In the case of neonatal screening, the question of the necessity of obtaining an explicit consent is debatable. Most countries that have established newborn genetic screening programs operate without the parents’ explicit consent. In the case of diseases that must be treated immediately, some consider screening to be a part of routine pediatric care and that obtaining explicit consent is therefore not necessary. Parents have a duty to act in their child's best interests. They have the right to be informed which diseases are screened for, as well as the goals and objectives of a newborn screening program. They may also refuse newborn screening if they wish.

Pediatric research in genetics raises particular ethical and legal concerns. Issues arise concerning consent and assent to research, the evaluation of risks and benefits of research, inclusion and exclusion criteria, confidentiality, and the return of results. There may also be issues surrounding the conservation and secondary use of genetic information (for example, during the formation of a biobank) as well as concerns regarding how to handle genetic information within families.

General issues linked with experimental techniques such as medical safety and child protection are often raised. In the particular context of reproductive cloning, there is also an aspect of social experimentation.

Many uncertainties remain, such as the status of human clones, the risk of discrimination, ambiguous relationships, confused personal identity and harmed psychological development. In fact, cloning seriously challenges the very notions of reproduction and family. Some are already proposing the adoption of a charter of rights for clones to prevent these potential problems.

In the short-term, results that reveal that a child is a carrier of a genetic mutation could give rise to stress and anxiety for the child and his/her parents, or even influence the parents’ perception of their child. A child's genetic information may also influence parental reproductive decisions. In the long-term, such results could lead to a decrease in self-esteem and affect family relationships.

Disclosure of carrier status information to the child’s parents could result in a breach of the child’s rights to privacy and confidentiality. For example, the parents could attempt to intervene in the child’s life decisions (choice of spouse, reproductive choices, etc.). Moreover, should parents opt to pass the information on to the child, this could breach the child’s “right not to know.” Yet for minors, genetic information, like all medical information, may be useful for making health, lifestyle and reproductive decisions.