Moving Beyond One-Size-Fits-All Healthcare To Personalised Medicine
Atlas Biomed
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Each of us is unique; medical treatment should reflect this
Every individual is unique at a genomic level, yet our treatment plans do not look all that different. Why? In short, many conditions are under-researched due to a scarcity of data. As a result, patients are treated as the average of the small group of people who participate in biomedical research.
A one-size-fits-all approach to medicine translates into long diagnosis times, ineffective treatment and inaccurate prognosis.
The future of healthcare is personalised
The completion of the Human Genome Project in April 2003 laid the foundation for "genomic medicine", and in turn, for the emergence of precision medicine.
Precision medicine is a model of healthcare that seeks to tailor treatment to individuals, displacing the current one-size-fits-all approach to healthcare. Also known as personalised medicine, it involves looking at patients’ genes, environment, and lifestyle to improve prognosis and treatment.
Large-scale genomic sequencing is driving personalised healthcare
Since the historic completion of The Human Genome Project, there has been a race to 0 in the cost of whole-genome sequencing. Currently, we can sequence a whole genome for around £500, a process that takes a day, excluding analysis. For reference, The Human Genome Project cost around $2.7 billion and spanned over a decade.
With these technological advances in genetic sequencing comes whole new possibilities, prime among them, the ability to create a massive database of diverse genetic information that researchers can share, analyse, and interpret.
Large scale whole-genome sequencing can reveal how genetic variants influence disease risk, uncover new conditions and explore how people respond to certain drugs (pharmacogenomics).
In practical terms, this can reduce the time it takes to diagnose illness, minimise the strain on healthcare systems and most importantly, save lives.
Whole-genome sequencing has already furnished promising results, most notably in the Genomic England 100,000 genomes project, completed in 2018. Building on previous successes, there are ongoing large-scale sequencing projects at both a national and international level.
The 100,000 Genomes Project By Genomics England
David Cameron announced the 100,000 genomes project in 2012, an ambitious program that offered whole-genome sequencing to 100,000 NHS patients with rare diseases or cancer. Genomics England was set up to deliver the flagship project – the first time that a national health care system offered whole genome sequencing to undiagnosed patients as part of routine care.
There were numerous challenges to delivering the project, including the sheer size of data being collected and managing the security of the sensitive information. Overall, the project was a resounding success and helped kickstart a UK genomics industry.
Since its completion, the data gathered has already furnished tangible benefits for patients. In a world-first study in the New England Journal Of Medicine, researchers analysed the genomes of 4,660 people from 2,183 families – all early participants in the 100,000 Genomes Project. Amazingly, this process led to a novel diagnosis in 25% of patients.
Better still, in a quarter of these cases, the sequencing resulted in more focused care, which improved health outcomes, including screening and vitamin supplementation. For those with intellectual disability, vision and hearing disorders, the diagnostic yield was as high as 40-55%.
The paper discusses multiple patient stories, all of which attest to the power of whole-genome sequencing to revolutionise healthcare and fuel the health breakthroughs of tomorrow. For instance, one ten-year-old girl in the program had undergone an arduous seven-year search for a diagnosis, during which she was hospitalised over 307 times at the cost of £356,571.
Whole-genome sequencing aided doctors in a diagnosis and led to a curative bone marrow transplant at the cost of £70,000. WGS also enabled predictive testing in her siblings, none of whom were found to be at risk.
In another case, WGS helped to retrospectively uncover a severe metabolic disorder in an infant who died at four months of age with no diagnosis. This discovery enabled researchers to test his younger brother within a week of his birth. They found that the younger brother suffered from the same disorder, allowing them to treat him with vitamin B12 injections and prevent complications.
As these case studies demonstrate, WGS has the power to uncover new diagnoses for those across a broad range of diseases. By doing so, WGS could free up essential services, save the NHS significant funds and shorten diagnoses times. In 2018, the secretary for health, Matt Hancock, committed genomics England to partially sequencing five million genomes by 2023 (genotyping).
All Of Us Program by National Institutes Of Health U.S.
The historic citizen science initiative All Of Us, run by the National Institutes Of Health, was begun in 2018 and is projected to last ten years. The project aims to sequence 1 million whole genomes across the U.S. To date, 463,000+ participants have enrolled, with over 320,000 having completed the initial steps of the program.
Like the 100,000 genomes project, the All Of Us program is advancing precision medicine by building an extensive database of genomic data, which will then be de-identified and shared with researchers and citizen scientists alike. This data will then be used to enable new scientific discoveries and initiate a shift towards precision medicine.
The project is unique in its breadth, diversity, access and innovation. For example, the participants submit wearables data, physical measurements and lifestyle questionnaires alongside a genomic sample, allowing researchers to understand how multiple factors influence the risk of complex diseases in conjunction with genetics.
Moreover, the program emphasises diversity, both in health status and ethnicity. By doing so, All Of Us aims to produce actionable medical insights for ethnic groups underrepresented in biomedical research previously. By closing the gaps in biomedical research, All Of Us has the potential to improve patient outcomes, from diagnosis to treatment and beyond.
What’s more, the database will help identify reasons for individual differences in response to commonly used drugs (pharmacogenomics). By identifying genetic reasons behind poor drug response, healthcare providers can give patients effective care quicker, without trial and error or unpleasant side effects.
The study is the biggest of its kind to date, meaning the analysis will be far more robust than the smaller studies preceding it. Essentially, the project is the biggest cohort study ever profiled.
Last but not least, the program is built to encourage impactful research, offering registered individuals a Research Workbench to conduct rapid hypothesis-driven studies. In theory, this tool could fuel new insights and catalyse the development of targeted drugs.
European Union 1 Million Genomes Initiative (1+MG)
An equally prodigious project is underway across Europe, seeking to enable interoperability between national genetic cohort data. The 1 million genomes project (1+MG) brings together 22 EU countries, plus the UK and Norway, with the goal of sequencing and sharing 1 million genomes across Europe by the end of 2022.
To achieve this end, the signatories collectively adopted the “1+MG Roadmap 2020”, which lays out three primary goals, including:
The Beyond 1 Million Genomes project oversees the implementation of the roadmap, offering coordination and support to signatories.
The 1+MG project will benefit people’s health in all member states and fuel groundbreaking research into cancer, rare and infectious diseases and metabolic disorders. For example, it can result in more effective treatment for cancer patients, reducing the risk of overtreatment or unnecessary side effects.
Moreover, whole-genome sequencing can help prevent both common and complex diseases by allowing researchers to identify harmful variants. The EU is developing polygenic risk score tests for multiple complex diseases based on the collected database.
Likewise, a federated, cross-border database will improve the prognosis for those with rare diseases. For example, suppose doctors encounter a patient with a rare disease and aren't sure which genes are responsible. In that case, they could launch a query through the EU database and discover others with a similar phenotype.
In the case of Martin, a Dublin national who experienced slow development and developmental abnormalities, doctors were able to find a similar case in Spain. After comparing their genomes, they discovered a common mutation and diagnosed both men with microcephaly, a condition that could be counteracted by supplementing a specific metabolite.
A final word
In short, the future of medicine is precision, whereby doctors can prescribe tailored treatments that consider a person’s genetic composition. Right now, there are multiple projects collating whole-genome sequences that can fuel health insights, increase the speed and accuracy of diagnoses and ultimately revolutionise healthcare for the better.
As the All of Us program demonstrates in America, citizen science initiatives will likely play a significant role in the shift towards precision medicine, especially in the mission to fill the data gaps present in biomedical research. What’s more, studies that treat the public as partners in clinical research instead of subjects can help drive medical breakthroughs and reinvent how we perform medical research.
Lastly, the 1+MG program is leading international collaboration and innovating new methods for secure data sharing. Not only can collaborative projects help straggling genomics industries to learn and develop, but they also multiply the amount of data collected, resulting in more robust analysis.
In conclusion, genomic sequencing can revolutionise healthcare, initiate the advent of precision medicine and fuel the health breakthroughs of tomorrow. The key challenges to realising this goal will be secure data-sharing and the development of biobank infrastructure to store genetic information.