Genetic counselling has been described as the process by which an individual fully understands and adapts to the contribution of genetic makeup in the medical and physiological state of the individual along with its influence on the familial implications of a disease condition [1]. Genomic medicine is at an all-time high in these years of fast developing technology in medicine [2]. The traditional process of genetic medicine and counselling involves the collection of data and interpretation of the history of pathology in the familial background of the individual along with the assessment of risks, informed consent, and psychosocial analysis of the individual [3,4]. The practice of genetic counselling belongs to the scope of functionality of several health care professionals and geneticists who carry out clinical practice [1]. Genetic counselling, is however, emerging as a separate field of science and is expected to take on a vast base in clinical practice. In the United States of America, genetic counselling is carried out for single-gene conditions. Genomic counselling is a rapidly developing field further to genetic counselling. Genomic counselling looks at studying the entire genomic sequence rather than the single-gene condition. Genomic counselling focuses on the entire genome sequence of the subject in question in order to make the medicine most effective. The application of genomic medicine in routine practice will directly influence the scope and approach of the genes. The process of the genetic medicine will also be directly influenced by the incorporation of genomic counselling in everyday medicine. Genomic counselling is further inexpensive to sequence the whole genome rather than single-gene sequences.
Introduction
Genomic sequencing and counselling are currently in practice and have been easing the challenge of cryptic disease symptoms and their unknown causes. Several familial diseases have existed in the past where the explanation of the causative factors to disease conditions is non-existent. This situation has been resolved with the advent of genomic medicine. The application of genomic medicine is ever-increasing and the enthusiasm about retrieving genetic information is also indefinite [2].
Genetic testing has been incessantly associated with uncertainty of information and unexplained phenomena. However, genomic medicine includes panel-, exome-, and whole-genome sequencing, which have further enhanced the likelihood of presence of uncertainty [5–11]. Uncertainty, as always, continue to be an inherent part of genomic medicine. The uncertainty of genomic medicine is also prevalent in its clinical and counselling dimensions as well; in terms of appropriately communicating the presence of uncertainty and preparing the individual for it. The communication has to be expansive when the information is uncertain.
Empirical research has provided important information and data on the approach of genomic medicine practitioners toward the uncertainty in everyday clinical practice. More often than not, there is an underlying negativity about the presence of uncertainty of information amongst most health care professionals in genomic medicine. Uncertainty is usually considered inherently harmful or pre-emptive in genomic medicine. This thought has spurred the assumption that such uncertainty is detrimental and has to be tamed or eradicated.
Literature that deals with such uncertainty associated with genomic medicine is largely also responsible for conveying the message that such uncertainty is frightening to physicians and thus it is projected in a negative light. What is lacking in the current state of affairs is the answer to the correct method of conception and acceptance of uncertainty in genomic medicine. The answer to this question is that the concept of negativity associated with the uncertainty of genomic medicine has to be removed from the system of genomic counselling. The theory that such uncertainty is almost always detrimental has to be rejected. While the influence of uncertainty on genomic medicine cannot be undermined, it is not necessarily problematic. The uncertainty of information in genetic medicine has to be incorporated into regular clinical practice with ease and perfection. The conceptualization of uncertainty in genomic medicine has to be developed and it has to be systematically and explicitly incorporated into the system of genomic testing. The ethically relevant concepts of welfare, autonomy, resilience, and solidarity in clinical genomic practice naturally gain importance with the incorporation of uncertainty into the genomic medicine practice.
The Conceptualization of such Uncertainty
The term uncertainty needs to be fully contemplated before the discussion on its importance is made. Uncertainty is in fact, a ‘cluster concept’ since it has several but mostly associated interpretations. In the broad sense, it is considered a state of possessing information that is either unknown or imperfect. The unknown information may also include incomplete information. As evident, the concept of genomic analysis possesses a sense of incomplete information gathering due to the fact that most of the times the collection of data relies on the interpretation of the genome. All the methods of obtaining genome sequence information have the inherent trait of uncertainty of information. In genomic sequencing, such incomplete information may arise in two major contexts namely – during diagnosis in a clinical setting and secondly during clinical prognosis of the condition.
The stages where the uncertainty has developed plays a vital role in determining the impact that it will have on the individual case. The information and its uncertainty is a property which is recognised in a subjective way or by experience in terms of the information given by the provider or the recipient; it may even be recognised sometimes as an objective property of the information itself or the result of the test. The following study assesses two formulations that are based on the conceptualisation of genomic uncertainty: Sources of uncertainty by Han et al and the forms of uncertainty by Babrow et al [2].
The study by Han et al looks at uncertainty in terms of the sources from which the information is derived. They use the parameters of probability ratio, ambiguity of information, and the complexity of the source or the information itself. They deduce that these sources are intrinsic in nature and that uncertainty is in fact an innate characteristic of information that is communicated in the process of genomic testing or counselling. The application of the taxonomy provided by Han et al is as follows:
Uncertainty and the probability of information occur when the outcomes of the future are either unknown or indeterminable. There are several instances in clinical practice where the patient is informed about how he/she is exposed to a ‘likely’ threat in terms of developing a disease – it can also mean that the probability of developing a particular disease is present. However, this information is indeterminable and does not predict future implications. This degree of uncertainty of information determines the regularity of the clinical practice and how this information would affect the individual. Thus the ethical concepts would then largely rely on the communication of the fact that the information is uncertain and that the patient may or may not develop the said disease or complication.
The ambiguity of information arises from this uncertainty of information as well. This occurs when the information is not precise or inaccurate. The evidence of the information is inaccurate and not precise or the whereabouts of the information and its source are unknown. It can also be a case of conflict in opinion regarding certain aspects. The genomic studies may indicate ambiguity in terms of genetic mutations, microdeletions, or SNPs and the likelihood of the occurrence of the disease. Once again, this information is accompanied by bouts of uncertainty and ambiguity of information.
The third component is the complexity of the uncertainty itself. The complexity of uncertainty occurs in the case where the information has inherent characteristics or features that make it complicated and indistinguishable. These features are innate factors including gene–gene interactions, reactions between the gene and the surrounding environment, epigenetic factors etc. These features also include pleitropy and penetration of an unknown nature in populations of the clinical area which are not previously tested or understood. In such clinical populations, the information will necessarily have the property of complexity of uncertainty [2].
The theory of Babrow et al is largely coherent with that of Han et al as described above. They have included a third, a fourth, and a fifth dimension to the concept of uncertainty and the implication of it on genomic medical practice. In these dimensions, they acknowledge the subjective or experiential aspects of uncertainty to a full extent.
Salient features of clinical practice of genomic medicine:
Paradigm shifts in clinical genomic counselling: Clinical genomic counselling and its practice are bound to witness and encounter a plethora of shifts in medical paradigms [12]. The largely important implication of this shift in paradigm is that it obscures the boundaries between the individual being already affected, or is likely to be affected, or simply at risk of procuring the disease or pathology. The paradigm shift is impactful to the clinical practice as it does not take into account the family history or other important parameters of disease prognosis and diagnosis. The practice of genomic medicine thus needs to break ground in establishing both theoretical and practical knowledge and expertise among practitioners of genomic medicine. The method of analysis and processes of classification and interpretation of genetic information needs to be understood fully by the practitioners.
Informed consent: Facilitators of genomic medicine and its practice need to be aligned to educate the individual subjects of the concept of informed consent for genomic sequencing. The consent is traditionally inclusive of the inherent risks, associated procedures, specific details, and the duration of time that the individual is expected to participate in the procedure. The consent has to include not just the particular or focused result of the test providing the indication of the specific condition, but also the secondary results and accompaniments of the result. Any incidental findings have also to be considered as a part of the consent process. Any incidental findings of the study also need to be considered while addressing the individuals for the result of the test. The range of these findings is immense and vast and includes a huge likelihood of ambiguity and difference of thought. The information is reliant on the subjective and objective scope for errors and the differences in the occurrence of the said pathology. The indispensable necessity here is that of providing adequate emotional context to the individual. Medical practitioners of genomic medicine are obliged to carry out the basic conveyance of the appropriate emotional context to the patient and the carer. Familial consent is also of much importance in the practice of genomic medicine [12].
A Case study:
Jennifer’s panel test: Jennifer is a 39-year-old female. She is fit and healthy at the time of examination. She has expressed concern about the status of the BRCA1 and BRCA2 gene and the possibility of mutation in those genes. She has derived this concern from the fact that her family history has instances of these mutations. She seeks genomic testing to validate this doubt. She is suggested a panel-testing of the genome along with testing 20 other cancer-related genes. The physician receives her consent for this testing procedure. Her test results indicate the absence of any BRCA1 or BRCA2 mutation. However, there is indication of a gene mutation responsible for cancer of the stomach. Her physician suggests that the medical intervention to reduce the risk of this implication is surgery where a large region of the stomach has to be surgically removed. As Jennifer does not have a family history of stomach cancer, she wishes to avoid surgery. This is a typical case where the genomic test result has uncertainty in terms of deciding the appropriate management of her condition. The prognosis is based on the absence of family history although the disease etiology is known. This case is a typical example of Han et al’s theory of complexity of uncertainty source and Babrow et al’s theory of uncertainty spurring from information structure and the test itself.
References
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