By Rachel Lim — Community Engagement Officer
For years, physicians have strived to consider the environmental, behavioural and genetic factors that may affect a patient’s health and disease management in order to provide precise and impactful care for each individual. However, it is only recently that we have been able to skyrocket this goal to the next level, with the term ‘personalised medicine’ rising to the forefront. Personalised medicine in the twenty-first century mainly refers to the use of genomics to optimise medical care and outcomes for each individual, enabling physicians to customise patient care in an unprecedented way. This approach has become prominent due to the exponential increase in the availability of genetic sequencing, testing, and data storage, accompanied by an increase in technological innovation and decrease in sequencing costs. This has enabled three major domains in clinical medicine to be accelerated, including the field of pharmacogenomics, genetic predispositions for common diseases, and the identification of rare disease-causing genetic variants.
Pharmacogenomics refers to the study of how genes modulate drug responses in different individuals. This is because variability of genes within the human population exists due to DNA polymorphisms and epigenetics. This causes changes in protein structure, function, or the amount of protein produced, which inevitably impacts how a person responds to a drug. Thus, if we are able to understand which DNA variants correspond to abnormal production of body proteins, we will be able to identify drug responders and non-responders, avoid adverse reaction events, and optimise drug dosage.
For example, 40% of metastatic colon cancer patients are unlikely to respond to the typical drugs prescribed for colon cancer such as cetuximab and panitumumab, because these patients have tumours with mutated KRAS genes. Hence, being able to identify patients who are unlikely to respond to these drugs will enable us to save time and increase their rate of survival by immediately prescribing an alternative drug which they are predicted to respond positively to. In particular, this is important in cancer where different individuals have different genetic mutations present in their tumours, and hence targeting an individual patient’s tumours allows us to maximise efficacy and treatment benefit, while limiting the risk of adverse side effects.
Certain genetic variants lead to an increase in an individual’s risk of developing a particular disease. Thus, valuable research has been conducted into genetic factors that when combined with other environmental factors, can result in the development of a common disease. For example, type one diabetes occurs due to immune-mediated destruction of insulin-producing beta cells, causing insulin deficiency which results in unattenuated blood glucose levels. Type one diabetes affects over 18 million individuals worldwide and there are on average seven new cases a day in Australia.
A genetic risk factor that has been identified which confers the highest risk of type one diabetes is having HLA-DQ2 and HLA-DQ8 alleles. It has been hypothesised that these alleles lead to the production of HLA molecules which do not interact properly with the body’s T cells in the thymus, thus allowing for self-reactive T cells to escape into the body’s periphery instead of being eliminated. Hence, if we can sequence a patient’s genome and identify these alleles, we can predict the patient’s risk of developing type one diabetes. With this powerful knowledge, physicians can more easily prescribe preventative measures to avoid the development of this condition. This allows for a shift in emphasis from reaction to prevention, in which we manage the root of the cause, rather than sticking to a Band-Aid solution. This can have a significant effect in reducing the costs generated by the disease burden on society, as well as individual health and economic costs on the patient and their family. Additionally, disease risk can be stratified so that high risk individuals are targeted more efficiently, allowing resources to be better utilised and early or prophylactic treatment to become more available.
Identifying rare disease-causing genetic variants
Rare genetic diseases collectively affect 25 million people globally and hence there is substantial merit in identifying genetic variants that cause these rare diseases. In Australia, a disease is considered rare if it affects less than 5 in 10,000 people. An example of a rare disease is cystic fibrosis (CF), in which the CFTR gene is mutated, subsequently affecting the production or function of the CFTR protein. This has a widespread impact throughout the body, resulting in many debilitating effects including lung disease, failure to thrive, and abnormal electrolyte composition in sweat. In fact, this condition has been recognised by midwives for hundreds of years by tasting the salty sweat on an infant’s brow, with the infamous saying that “an infant that tastes of salt will surely die”.
Fortunately, we have made leaps and bounds in identifying the genetic cause and consequences of cystic fibrosis, and the median life expectancy of people with CF has increased from a few months in the 1950s to over 40 years of age presently. Scientists have also created cystic fibrosis gene panels to detect the 175 most common genetic variants that cause cystic fibrosis, and this screening test can be performed on infants so that early treatment and management can commence promptly for affected newborns.
Considerations and drawbacks
Despite the many benefits and potential of personalised medicine, there are also several issues and challenges that we need to consider. For instance, infrastructure requirements such as the collection and storage of genomic data are a major hurdle. At the moment, we do not have sufficiently large, secure databases to store such information, nor is there enough funding and research going into this technological challenge. Additionally, there are privacy and ethical issues that arise as the genetic information of an individual is very personal and sensitive material that larger and more powerful organisations might exploit. There are also legal disputes as to who owns the genomic data collected and who is allowed access; questions that we must consider and create laws to govern.
Another major issue is the potential of personalised medicine to exacerbate inequalities. Although the cost of genomic sequencing is decreasing, there are still significant expenses that must go into the collection, sequencing, and interpretation of genomic data. Hence, it is foreseeable that equal access and affordability may not be available initially, which can drive increased disparities between countries and different socioeconomic groups. Considering the substantial benefits of personalised medicine, this may lead to a deepened poverty cycle which may spiral to become inescapable.
Personalised medicine is still a developing approach to clinical medicine that has a bright prospect in the future, despite its issues and challenges. It signifies a momentous change in patient care that aligns with the rise of the Information Age, and places us in a position to employ preventative medicine and improve the quality of life for patients. Moving forward, personalised medicine can be largely enabled by electronic health records, which will allow clinicians and patients to share and integrate relevant genomic information, supporting interdisciplinary care and management. Adequate regulatory frameworks and data management protocols must be established to protect personal rights and secure health data flow.
Additionally, healthcare training in technology, data analysis and genomic interpretation must be prioritised so that healthcare workers are able to understand and communicate this information to patients and the wider public. There is also an accompanying need for an increase in general health literacy so that patients have a greater awareness of their choices and are able to understand and appropriately consent to their desired management plan. Thus, it is through innovation, regulatory frameworks, education and commitment to equal access that personalised medicine will truly thrive and have a profound impact on healthcare globally.