Genomic medicine (also known as precision medicine or personalised medicine) uses an individual's genetic information to help guide healthcare providers about genetic contributions to a patient's health, susceptibility or resilience to disease, or their response to therapeutic interventions. The aim is to inform preventative strategies and/or treatments likely to be of most benefit to patients, in an individualised manner.
What is medical genetics?
Medical genetics is any application of genetic principles to medical practice. Currently, this includes studies of inheritance, mapping disease genes, diagnosis and treatment, genetic impacts on responses to drugs (see pharmacogenomics) and genetic counselling. Increasingly, these aspects of medical genetics are being brought together to tailor precision medicine to health as it applies to the individual patient.
Stratified medicine is based on identifying subgroups of people with distinct mechanisms of disease or particular responses to treatments. A stratified approach to genomic medicine provides a deeper understanding of the effect of the disease on different patient subgroups, so the right treatment can be identified, developed and delivered at the right time for each group.
How does precision medicine work?
The complete set of genetic instructions for a person is called their genome. While the vast majority of our genetic code is identical among all peoples, some changes occurred as humans spread across the globe. Comparing and understanding these variations in the genome helps identify genes responsible for population and individual-specific differences in health and the risk of disease.
Precision medicine focuses on sequencing and then analysing an individual’s genome to look for variations that might contribute to disease by altering the activity or expression of genes and the function of the proteins they encode. In some cases, these variations might not be inherited, but rather are new (de novo) changes that occurred during the very early development of a particular individual or later in their life as cells continue to multiply.
Sequencing is a technique that establishes the order of the DNA base-pairs that make up a person’s genes. In much the same way that the order of binary 1’s and 0’s forms the basic code for information in a computer, the sequence of four DNA bases in the human genome (represented by the symbols A, C, G and T) provides the building blocks for genes and instructions for the way those genes interact in different cell types of the body. Understanding the three billion-long sequence of genomic DNA base pairs can help to reveal the influences of environment, lifestyle and heredity on health.
Information from interactions between genes and environmental factors is used to design diagnostic methods and treatment protocols to tailor a patient’s clinical care - the detailed genetic information gained from genomic sequencing is effectively a more precise way of noting the family history and the influence that heritable factors might have on that person’s health.
Personalised medicine draws on datasets from large research knowledge databases, including the reference Human Genome, to compare with the genome of an individual patient. These databases are a primary source of data about human reference sequences, human sequence variation and functional implications across populations; they contain aggregate genomic information, not patient-level data.
What does precision medicine mean for the patient?
Personalised medicine customises health care. An individual’s genetic profile can have a significant impact on what treatments are used to treat inherited disorders and chronic diseases such as heart disease, cancer, diabetes and respiratory diseases, and how effective that could be. It can help decision-making.
Importantly, it also directs preventative and pre-emptive care for those at risk for disease - wellness genomics is a new and rapidly growing field of health care. Ultimately, personalised wellness will help a patient find solutions for their own nutrition, exercise and mental wellbeing based on genetic profile and predispositions.
Are genomic treatments publicly available now?
Globally, genomic medicine has started to transition from research into clinical practice; there are several large initiatives to sequence human genomes and use the results in clinical care, including projects in the USA and Europe to each sequence one million genomes and a 500,000 Genomes Project in the U.K.
Currently, treatment of only a small number of inherited diseases and conditions draws on genetic information to guide medical decisions, but this form of clinical care is expanding rapidly into other common disorders. This includes assessing disease risk in individuals and their families, diagnosing rare and undiagnosed diseases, and improving drug safety and efficacy.
Benefits for Aotearoa
Understanding the DNA sequence variations that play a role in a patient's health, disease or condition will enable New Zealand health practitioners to more accurately predict which of the treatments available here will be most effective and safe, and tailor diagnostic and treatment decisions. This will also help in prevention of health issues directly affecting New Zealanders, such as heart disease.
How will genomic medicine benefit Māori health?
Our unique cultural composition means that we can’t simply copy infrastructure and rely on data from overseas health genomics initiatives. It is therefore a health imperative to catalogue the characteristics of the genomes of New Zealanders, with an emphasis on peoples with Māori and Polynesian ancestry.
New Zealand-specific information will enhance current health initiatives, particularly for indigenous populations currently underrepresented in genomic data, thereby reducing some healthcare disparities. There is a Treaty of Waitangi obligation to ensure new healthcare technologies are available to all.
Managing genomic data in a culturally appropriate way is crucial to develop the population information we need to deliver New Zealand-centric genomic medicine. Respecting whakapapa, a fundamental principle in Māori culture, has strong significance to collecting this genomic information. All genomic healthcare and research must protect the rights, interests and taonga of Māori, and respect the view of Māori that DNA samples and the data generated from them have significant links with cultural practice and whakapapa.
What precision medicine is currently available in Aotearoa?
Globally, health care models are beginning to change towards offering more targeted medical tests and treatments. However, although some genomic testing is being done in New Zealand, most health practitioners do not yet have the systems or knowledge to incorporate this into routine health practice. (Genomic testing investigates multiple genes at once, useful when there are a number of genes which can cause a condition or it is unknown which gene may be the cause.)
The most active areas of clinical genomics use in New Zealand are in oncology and paediatric genetics. An example of the potential benefit of precision medicine to patients is genetic testing for genes with sequence variations increasing the risk of familial breast, bowel or stomach cancers. Through genetic testing, early identification of the presence of one of these variant genes in a patient can help inform their decision about undergoing potentially life-saving preventative surgery.
Aotearoa-specific research and development is needed
New Zealand-specific solutions will require coherent national processes to bring together genomic precision health data from research and practice. A scalable national genomics research infrastructure that includes a New Zealand genomic database is currently being developed. This resource will provide the genomic information and tools to support genetic testing in New Zealand. Capability in interpreting and applying genomic sequence data will need to be developed for front-line health practitioners to use this information as a decision-making tool for individual patient care as part of their routine practice.
The Treaty of Waitangi provides the framework for active protection of Māori interests, rights, authorities and valued things. Māori knowledge systems are maintained, held, utilised and governed within the regime of traditional Māori authority holders. Kaitiakitanga, which means guardianship, is a way of managing the environment based on the Māori world view. Iwi are kaitiaki of their information and therefore can be intimately involved in decisions regarding the use of genetic data.
How do people get genetically tested?
Genome sequences originate from DNA. DNA is extracted in a laboratory from either blood or saliva samples obtained from patients. Lab technicians then look for specific patterns or changes in that DNA base-pair code information, which is stored on a computer database. Evaluating the genetic information and interpreting their implications requires specialist skills, and is carried out by clinical geneticists, genetic pathologists and genetic counsellors.
Genetic counsellors are health practitioners with specific training in communication and genetic science who bridge the gap between patient and treatment. Their role includes preparing patents for genetic testing, communicating the results, helping patients understand options for managing genetic conditions and supporting the individual to talk to relatives at risk of the same disease.
Is DNA testing for precision medicine safe?
There is very little health risk associated with providing a DNA sample.
The quality and level of evidence underpinning interpretation of the data from a DNA sample can vary enormously. Genetic testing is still developing and interpretation of which DNA sequence variations contribute to medical conditions is an area of ongoing research. This area of knowledge is at its most underdeveloped for individuals with non-European, non-Asian genetic heritage. Results from a patient’s personal genomic profile will therefore usually not provide all the answers for diagnosis or disease treatment.
Additionally, the regulations and protocols supporting the storage and use of this data need to meet the highest levels of health data security for genomic precision medicine to be considered safe.
What happens to a patient’s data?
Patient data must be stored securely. Regulations for consent, access and protection of an individual’s genetic profile vary across the world; most countries have some privacy controls to prevent data mis-use. In some countries individual genetic data, obtained either for medical purposes or as an ancestry test, may be shared with a medical research knowledge database for public benefit. This information is usually depersonalised and anonymous. In New Zealand, it is important that biological samples and DNA from Māori is respected as taonga and access to that data is therefore managed and not open-source.
Issues for genomic medicine in New Zealand
Quality information is essential to inform clinical care. New Zealand’s implementation of genomic technologies in health is currently dependent on European-based data and we need to build our New Zealand-specific genomic knowledge base.
It’s important that New Zealand continues to develop national research capability to ensure ownership, protection and governance of the use of our own genetic information - particularly our biological whakapapa and our taonga. We are then not vulnerable to international genetic data initiatives that operate with different rules for access, privacy and use of personal genomic information.
Data uses and misuse is an ongoing global challenge and legislative protection for the individual consumer varies from country to country. Informed consent is crucial; New Zealand consumers need to understand the privacy risks for individuals sharing DNA with international ancestry or consumer genetic-testing companies and check how information is used, shared and stored.