Predictive Genetic Testing

I. Introduction

The term "genetic testing" and "genetic examination" encompasses various methods that can provide direct insights into the genetic make-up of an organism, also known as its genome . Genetic tests involve the analysis of genes or genetic products. Other methods are available, without DNA analysis, which can be used to obtain information about the genetic constitution of a human being: they include imaging techniques such as X-ray and computer tomography or indeed the mere appearance of a person. Kidneys dotted with numerous cysts, for example, can indicate the presence of a particular hereditary kidney disease.
Genetic tests are examinations conducted for the targeted detection of disease-causing (pathogenic) changes or mutations in DNA. In addition to this primary purpose, genetic tests in the form of so-called direct-to-consumer-tests can also be used to establish traits that do not have any disease status.

Postnatal predictive diagnostics is used to identify genes or genetic defects that can lead to disease in later life or dispose a predisposition to such disease. In this context, genetic tests performed in childhood and adulthood (postnatal examinations) should be distinguished from those carried out before birth (prenatal), before implantation (preimplantation diagnostics) or on polocytes (polar body diagnostics). Further information can be found in the In Focus Preimplantation Genetic Diagnosis. Classification is determined by the point in time when such testing is performed.
A genetic test is referred to as predictive if the examination is performed on a person who does not exhibit any symptoms of disease at the time of testing.
Genetic diagnostics used in the context of a tentative clinical diagnosis are thus not included in predictive testing methods. In this instance, a genetic test is performed on an already sick individual in order to confirm or discard a previously presumed diagnosis; thus, for example, a case of unclear childhood myopathy can be diagnosed as spinal muscular atrophy with the aid of molecular genetic testing.
Predictive genetic testing can be used to investigate whether a mutation is present that indicates a predisposition to a disease.
Gene mutations are changes in the genetic information on a segment of DNA that codes for a specific protein. Such a change can occur spontaneously or it may be environmentally induced. Environmentally induced mutations are triggered by environmental factors, such as radioactive or other ultraviolet radiation.
Individuals who test positive, however, need not necessarily become diseased. More than 90% of all mutations have absolutely no effect on the phenotype of a living organism they are harmless. These are also described as "neutral mutations" which affect exclusively the genotype.
Under 10% of all mutations have a more or less strong effect on the phenotype and can lead to diseases. The extent to which a trait is actually expressed in a specific case is referred to as penetrance. Various studies can be carried out using the same genetic methods. These studies may differ in terms of the informative value and the quality of the data collected as well as the intended purposes.
Various types of tests are as follows:

  • Predictive diagnostics in a strict sense on the basis of which the presence of a genetic predisposition can be diagnosed before the onset of a disease.
  • Heterozygote tests which investigate whether the status of genetic carrier (heterozygosity) is present, from which autosomal recessive or X-linked recessive inheritance of a disease can be inferred. They should be differentiated from screening programmes which screen larger groups of people – for example specific risk groups or entire populations – rather than individual persons for genetic carriers.
  • Pharmacogenetic tests which can provide information about a genetically determined, individual tolerance of drugs and susceptibility test with the aid of which intolerances to certain substances can be established. These intolerances can be environmental as well as genetic.

The German Genetic Diagnostics Act (GenDG)

Following a long and intense discussion - both in the specialist disciplines involved and in politics - as well as several political initiatives the German Bundestag passed the law on genetic testing of humans Genetic Diagnostics Act - (GenDG) regulating the use of predictive genetic testing in Germany, on 24 April, 2009. The German Genetic Diagnostics Act entered into force on 1 February, 2010 (§ 27).

The Act explicitly aims at defining the prerequisites for genetic testing and genetic analysis performed in the context of genetic testing, as well as for the use of genetic samples and data, and at preventing discrimination on grounds of genetic predisposition, in order to ensure the state's commitment to respect and to protect human dignity and the right to informational self-determination (§ 1).
The scope of the Act is not limited to predictive genetic testing: it extends, in fact, to genetic testing carried out on (born) human beings (i.e. postnatal) as well as to genetic examination of embryos and foetuses (prenatal; see special provisions in § 15).
A core objective of the GenDG is to ban discrimination on grounds of one's own genetic predisposition or that of a genetically related person, due to undergoing or not undergoing a genetic test or analysis, or due to the results of such a test or analysis (§ 4 para. 1). Moreover, the Act provides for measures to promote quality assurance in the field of genetic analysis (§ 5), stipulating in particular that institutions performing genetic testing must be specifically accredited.
Genetic testing for medical purposes may only be carried out by a physician ("Arztvorbehalt" § 7). While diagnostic testing may be conducted by a general practitioner, predictive testing must be performed by a medical specialist. Furthermore, the informed consent of the person concerned is a necessary prerequisite to legally perform genetic testing (§ 8). Prior to giving consent, the person concerned shall be informed of the nature, significance and consequences of the genetic test to be performed (§ 9). Performing genetic testing on persons unable to give consent shall only be allowed under certain conditions (§ 14). Moreover, the Act contains provisions relating to genetic counselling (§ 10) and to disclosure of the results of genetic tests (§ 11). In the case of predictive genetic testing, the person concerned shall receive genetic counselling from a doctor with specific qualifications before the test is performed and once the results are on hand, unless this person - after having received written information on the contents of the counselling - has waived their right to genetic counselling in writing. After counselling, the person concerned shall be allowed adequate time for consideration before undergoing the test (§ 10 para. 2).
Restrictive provisions apply to the use of genetic testing in connection with access to insurance: neither before nor after the conclusion of an insurance contract may insurance providers require the insured to undergo genetic testing or analysis (§ 18 para.1 no. 1). Furthermore, insurers are not entitled to demand the disclosure of results from an earlier genetic test or analysis, and they may not receive or use such results or data (§ 18 para. 1 no. 2). However, this general prohibition does not apply to life insurance, occupational disability insurance, general disability insurance and care pension insurance if the agreed insurance value amounts to more than EUR 300,000 or an annual pension of more than EUR 30,000.
With regard to working life, the use of genetic testing is also subject to strict limitations: in particular, employers may not require employees to undergo genetic testing or analysis, neither before nor after the conclusion of an employment contract (§ 19 para. 1). By the same token, they are not entitled to demand the disclosure of results from an earlier genetic tests or analysis, or receive or use such results (§ 19 para. 2). Separate provisions exist for the use of genetic testing in the context of occupational safety and health (§ 20).
Finally, the Act provides for the establishment of a multidisciplinary independent genetic diagnostics committee at the Robert Koch Institute, composed by 13 experts from the disciplines of medicine and biology, two experts from the disciplines of ethics and law, as well as two representatives of leading patient and consumer advocacy groups. The members and deputy members of the committee are appointed by the Federal Ministry of Health for a period of three years (§ 23 para. 1). The tasks of the genetic diagnostics committee include, amongst others, the development of guidelines regarding the state-of-the-art of science and technology, pertaining to qualification requirements for genetic counselling and to requirements regarding the content of information and genetic counselling. Moreover, if requested by individuals or institutions conducting genetic testing or analysis, the committee may deliver an expert opinion on specific questions regarding the interpretation and implementation of these guidelines (§ 23 para. 5). Finally, the committee submits every three years a progress report published by the Robert Koch Institute (§ 23 para. 4). These regulations shall help to continuously assesses and evaluate the development in genetic diagnostics.

The German Ethics Council
The German Ethics Council (earlier the National German Council) dealt with the subject of predictive genetic testing already in 2007 and published in this context its opinion on “Predictive health information in the conclusion of insurance contracts". Since the methods of the genetic analysis have been rapidly advanced in the last years and, as a result of this development, profound social questions have been posed, the Federal Government requested the German Ethics Council to deliver another extensive opinion on the future of the genetic diagnostics. To fulfill this task, the German Ethics Council published in April 2013 an opinion with the title "The future of genetic diagnosis – from research to clinical practice" . The Ethics Council believes that there is an additional legal and social need for action beyond the law of genetic diagnosis that came into force in 2010 and declares detailed recommendations both on genetic diagnosis in general and on prenatal diagnosis. Recommended among others are: the establishment of a public information platform on the internet for the available gene tests, the impact and significance of these tests, the conduction of genetic testing and the incorporation of ways to handle the results into the medical training and advanced education. Moreover concrete extensions of the law of genetic diagnosis (GenDG) are required by means of which obscurities regarding, among others, the clarification and counseling, gene tests for medical purposes with persons who are unable to consent, newborn screening and gene tests for non-medical purposes should be resolved. To reduce the personal risk of direct-to-consumer-tests which are generally not allowed in Germany, the German Ethics Council calls for the arrangement for additional consumer clarification, the regulation of consumer protection as well as for the initiative of the Federal Government and the EU-wide common regulations. Within the area of prenatal diagnosis, the German Ethics Council recommends the consideration of the psychological situation of pregnant women upon informing them about the possibility of prenatal diagnosis and also to consider mentioning the option of non-utilization. Moreover, prenatal diagnosis should only be performed by specialized institutions, since an adequate care is only possible through the collaboration with organizations such as a psychosocial counseling center.

II. Ethical Aspects

Predictive genetic tests have great potential to promote health. They enable the predisposition to a treatable disease to be identified at an early stage. Pharmacogenetic tests may also open up the option of identifying a genetically related sensitivity to particular active pharmaceutical agents, which makes it possible to individually tailor the dosage and selection of medication. Yet predictive genetic testing methods are associated not only with opportunities, but also with risks. The identification of these risks is of central importance to the ethical evaluation of predictive genetic tests. The following risks, in particular, are mentioned specifically in the ethical debate surrounding predictive genetic tests.

Violation of the right to informational self-determination

Genetic data can touch upon the core areas of an individual's personality. It can therefore be considered to be generally accepted that as far as their own genetic constitution is concerned every individual is entitled to a "right to know" as well as a "right not to know". Both are commonly subsumed under the concept of "informational self-determination". Problems arise in cases where one person's right not to know collides with another person's right to know. For instance, test results which also include information about the genetic constitution of biological relatives or the analysis of personal genetic data in so-called human biobanks for research.

Intrafamilial conflicts

Genetic data always additionally contain information about the biological relatives of a tested person. This circumstance can lead to special conflict situations within families. If a person tests positive, this test result can at the same time be used to draw conclusions about the genetic constitution of a biological relative. If, for example, somebody with a grandparent suffering from Huntington's disease tests positive for the relevant genetic mutation, it is then certain that the corresponding parent also carries this genetic mutation. In other words, the right to know of the tested person can collide with a biological relative's right not to know.

Psychological strains due to positive test results

If a predictive genetic test establishes that a person has a hereditary disease, this can result in considerable psychological strains for the affected person. Such strains can be exacerbated by the complexity typically associated with the results of genetic tests: especially if a disorder displays only low penetrance or highly variable expressivity it is difficult to decide on an appropriate approach. Recent research results in this respect show that only few persons use the opportunity of changing their behaviour in reaction to predictive examination results. Even if this does not necessarily reveal something about the psychological state of the persons in question, the minor impact of these test results should be cause for a careful consideration of the argument of psychological pressure through positive test results in the case of predicative procedures.

Risk of "geneticising" the living world

The term "geneticising" is generally used to refer to a process in which differences between individuals are reduced to their DNA, i.e. in the course of genetification diseases and behaviours are increasingly perceived as being genetically based. Geneticisation presents a problem if it culminates in genetic determinism, which asserts that a person can be determined entirely by their genes.

Genetic discrimination

The term "discrimination" denotes disadvantageous treatment of people on the basis of traits that for the facts and circumstances in question are irrelevant. In connection with predictive genetic tests, there is a risk that a person who tests positive may be considered a "healthy invalid", which can lead to social disadvantages within society. Although no symptoms whatsoever are present, the affected subjects are often perceived as sick and hence treated accordingly. This form of "genetic discrimination" can be particularly problematic with an eye to insurance and employment relationships.

There is a far-reaching consensus that predictive genetic testing methods present both opportunities and risks from an ethical perspective. Consequently, the ethical debate is concerned not least with analysing regulatory models with an eye to determining whether they lend themselves to minimising the risks associated with predictive genetic tests, without simultaneously restricting the opportunities that such tests offer. Four prototypical regulatory models, in particular, can be distinguished in the debate:

Regulatory models

1. Licensing procedure
The licensing procedure is a regulatory model that requires the definition of quality standards for predictive genetic tests in view of the potential risks outlined above. In this model, the individual can only really exercise his or her right to informational self-determination and decide for or against a test if it is ensured that a test provides a reliable informational basis. Licensing procedures could be put in place not only for the tests themselves, but also for the laboratories that analyse the tests and for those that convey the test results. There is now a broad consensus that licensing procedures make sense in the context of predictive genetic tests. Yet there is also debate, firstly, as to whether the requirement for a licence should be applicable to all tests or only to those, the results of which can give rise to severe psychological strains, and secondly, as to whether and how this model must be complemented by other regulatory models.

2. Anti-discrimination regulations
An anti-discrimination regulation as a regulatory model for predictive genetic tests has been proposed by those who believe that the use of testing itself should not be at the core of a regulatory regime, but rather the way in which genetic data are used. Only if genetic differences are turned into the basis for social exclusion, proponents of this model argue, is there a risk situation that needs to be regulated. Critics, on the other hand, object that the concept of genetic discrimination is difficult to define and should not therefore be elevated to the basis for regulation. What is more, they assert that not all the risks associated with genetic tests would be covered by such a model.

3. Physician's prerogative
A further regulatory model, namely that of the physician's prerogative envisages that all or at least some predictive genetic tests should only be carried out by physicians or possibly even only by specialists in human genetics.
Advocates of this model are aiming at preventing the commercialization of genetic tests, such as the merchandise of direct-to-consumer-tests and the adjunctive consequences. They advert that solely the physician's medical competence can guarantee an appropriate consultation prior to a possible test as well as the correct interpretation of test results. 

Furthermore, medical confidentiality would ensure that genetic data could not be communicated to others in other words, data protection could be guaranteed by way of the physician's prerogative.
Problems arise, however, when the performance of non-disease-related tests so-called "lifestyle" tests is involved. If it were compulsory to consult a physician for this type of genetic examination, physicians would take on the role of general life advisors - something which in fact should not be their task.

4. Linkage to health purposes
A widely discussed regulatory model, that of linkage to health purposes is contained in the Council of Europe's Convention on Human Rights and Medicine. Article 12 states:

"Tests which are predictive of genetic diseases or which serve either to identify the subject as a carrier of a gene responsible for a disease or to detect a genetic predisposition or susceptibility to a disease may be performed only for health purposes or for scientific research linked to health purposes, and subject to appropriate genetic counselling."
By restricting genetic tests in this way to health purposes the Council of Europe is seeking to ward off unjustified third-party interests in genetic data, such as those of employers or insurance companies. Thus, only a direct medical benefit could be cited as justification for the performance of a predictive genetic test. Yet critics doubt whether the concept of "health purposes" could be defined with adequate precision. If this is not the case, such an attempt at regulation risks becoming shapeless.

Suggested citation

German Reference Centre for Ethics in the Life Sciences (2024): In Focus: Predictive Genetic Testing. URL [date of access]

Wird geladen